Closure device and methods for making and using them

ABSTRACT

A medical device that includes a plurality of strut members forming a plurality of generally diamond-shaped openings, the plurality of strut member being configured to form an annular shaped structure with the generally diamond-shaped openings extending generally longitudinally relative to a longitudinal axis of the medical device. A plurality of tissue engaging portions are associated with the plurality of struts, with each tissue engaging portion extending towards the longitudinal axis in a deployed configuration.

CROSS-REFERENCE TO RELATED APPLICATIONS

This a continuation application of U.S. patent application Ser. No.11/396,141, filed 31 Mar. 2006, now U.S. Pat. No. 8,690,910 which is (i)a continuation-in-part application of U.S. patent application Ser. No.10/787,073, filed Feb. 24, 2004, now U.S. Pat. No. 7,806,904, which is acontinuation-in-part application of U.S. patent application Ser. No.10/435,104, filed May 9, 2003, now U.S. Pat. No. 7,879,071, which is adivisional application of U.S. patent application Ser. No. 10/081,726,filed Feb. 21, 2002, now U.S. Pat. No. 6,623,510, which is acontinuation-in-part application of U.S. patent application Ser. No.09/732,178, filed Dec. 7, 2000, now U.S. Pat. No. 6,719,777, and (ii) isalso a continuation-in-part application of U.S. patent application Ser.No. 10/335,075, filed Dec. 31, 2002, now U.S. Pat. No. 7,211,101, whichis a continuation-in-part application of U.S. patent application Ser.No. 10/081,726, filed Feb. 21, 2002, now U.S. Pat. No. 6,623,510, whichis a continuation-in-part application of U.S. patent application Ser.No. 09/732,178, filed Dec. 7, 2000, now U.S. Pat. No. 6,719,777, each ofthe disclosures of which, and any references therein, are incorporatedherein in their entirety by this reference.

This continuation application also relates to U.S. application Ser. No.09/732,178, filed Dec. 7, 2000, now U.S. Pat. No. 6,719,777; Ser. No.10/081,726, filed Feb. 21, 2002, now U.S. Pat. No. 6,623,510; Ser. No.10/335,075, filed Dec. 31, 2002; Ser. No. 10/081,723, filed Feb. 21,2002, now U.S. Pat. No. 6,942,674; Ser. No. 10/081,717, filed Feb. 21,2002; Ser. No. 10/356,214, filed Jan. 30, 2003 and Ser. No. 10/638,115,filed Aug. 8, 2003, the disclosures of which, and any referencestherein, are incorporated herein in their entirety by this reference.

BACKGROUND OF THE INVENTION

1. The Field of the Invention

The present invention relates generally to apparatus and methods forengaging tissue and/or closing openings through tissue, and moreparticularly to devices for closing a puncture in a blood vessel orother body lumen formed during a diagnostic or therapeutic procedure,and to methods for making and using such devices.

2. The Relevant Technology

Catheterization and interventional procedures, such as angioplasty orstenting, generally are performed by inserting a hollow needle through apatient's skin and intervening tissue into the vascular system. A guidewire may then be passed through the needle lumen into the patient'sblood vessel accessed by the needle. The needle may be removed, and anintroducer sheath may be advanced over the guide wire into the vessel,e.g., in conjunction with or subsequent to a dilator. A catheter orother device may then be advanced through a lumen of the introducersheath and over the guide wire into a position for performing a medicalprocedure. Thus, the introducer sheath may facilitate introduction ofvarious devices into the vessel, while minimizing trauma to the vesselwall and/or minimizing blood loss during a procedure.

Upon completion of the procedure, the devices and introducer sheath maybe removed, leaving a puncture site in the vessel wall. Externalpressure may be applied to the puncture site until clotting and woundsealing occur. This procedure, however, may be time consuming andexpensive, requiring as much as an hour of a physician's or nurse'stime. It is also uncomfortable for the patient, and requires that thepatient remain immobilized in the operating room, catheter lab, orholding area. In addition, a risk of hematoma exists from bleedingbefore hemostasis occurs.

Various apparatus have been suggested for percutaneously sealing avascular puncture by occluding the puncture site. For example, U.S. Pat.Nos. 5,192,302 and 5,222,974, issued to Kensey et al., describe the useof a biodegradable plug that may be delivered through an introducersheath into a puncture site. When deployed, the plug may seal the vesseland provide hemostasis. Such devices, however, may be difficult toposition properly with respect to the vessel, which may be particularlysignificant since it is generally undesirable to expose the plugmaterial, e.g., collagen, within the bloodstream, where it may floatdownstream and risk causing an embolism.

Another technique has been suggested that involves percutaneouslysuturing the puncture site, such as that disclosed in U.S. Pat. No.5,304,184, issued to Hathaway et al. Percutaneous suturing devices,however, may require significant skill by the user, and may bemechanically complex and expensive to manufacture.

U.S. Pat. No. 5,478,354, issued to Tovey et al., discloses a surgicalfastener including an annular base having legs that, in a relaxed state,extend in a direction substantially perpendicular to a plane defined bythe base and slightly inwards toward one another. During use, thefastener is fit around the outside of a cannula, thereby deflecting thelegs outward. The cannula is placed in an incision, and the fastener isslid along the cannula until the legs pierce into skin tissue. When thecannula is withdrawn, the legs move towards one another back to therelaxed state to close the incision.

U.S. Pat. Nos. 5,007,921 and 5,026,390, issued to Brown, disclosestaples that may be used to close a wound or incision. In oneembodiment, an “S” shaped staple is disclosed that includes barbs thatmay be engaged into tissue on either side of the wound. In anotherembodiment, a ring-shaped staple is disclosed that includes barbs thatproject from the ring. Sides of the ring may be squeezed to separate thebarbs further, and the barbs may be engaged into tissue on either sideof a wound. The sides may then be released, causing the barbs to returncloser together, and thereby pulling the tissue closed over the wound.These staples, however, have a large cross-sectional profile andtherefore may not be easy to deliver through a percutaneous site toclose an opening in a vessel wall.

Accordingly, devices for engaging tissue, e.g., to close a vascularpuncture site, would be considered useful.

BRIEF SUMMARY OF THE INVENTION

The present invention is directed to devices and methods for engagingtissue, e.g., to connect tissue segments together or to close and/orseal openings through tissue, such as in a wall of a body lumen. Moreparticularly, the present invention is directed to vascular closuredevices or dips for closing a puncture in a wall of a blood vesselformed during a diagnostic or therapeutic procedure, and to methods formaking and using such devices.

In accordance with one aspect of the present invention, a device forclosing an opening in a body lumen is provided that includes a generallyannular-shaped body defining a plane, and a plurality of tissue engagingportions extending from the annular-shaped body substantiallytransversely with respect to the plane. In this embodiment, opposingtissue engaging portions, e.g., tines, are biased towards asubstantially planar configuration lying in the plane. In oneembodiment, the tissue engaging portions are biased towards one another,e.g., to close a puncture site or other opening through tissue.Alternatively, the tissue engaging portions may be biased away from oneanother.

In accordance with one aspect, the tissue engaging portions areintegrally formed with the annular-shaped body, e.g., from a sheet ofmaterial, such as Nitinol or other superelastic alloy. The tissueengaging portions may be formed with the sheet of material in thesubstantially planar configuration. The tissue engaging portions may bedeflected substantially transversely with respect to the plane to definea substantially transverse configuration. Alternatively, the device maybe formed from an elongate wire or tube that may be wound to form anenclosed body.

In accordance with another aspect, the tissue engaging portions, e.g.,tines, optionally including barbs, for penetrating tissue, may bedisposed substantially symmetrically about a central axis.Alternatively, the tissue engaging portions may be disposed in opposingsets along a linear axis.

In accordance with another aspect of the present invention, a device forengaging tissue, e.g., to close an opening in a body lumen, is providedthat includes a generally annular-shaped body defining a plane. Aplurality of tissue engaging portions extend from the annular-shapedbody substantially transversely with respect to the plane. In oneembodiment, opposing tissue engaging portions of the device are biasedtowards a substantially planar configuration lying in the plane, asdescribed above.

One or more expandable elements are disposed along a periphery of theannular-shaped body. The expandable elements are expandable betweenexpanded and compressed states for increasing and reducing a peripheraldimension of the annular-shaped body, respectively. In one embodiment,the expandable elements may be an enclosed cell, e.g. a diamond-shapedcell, having a first width in the expanded state and a second width inthe compressed state that is smaller than the first width.Alternatively, the expandable elements may be a zig-zag element or anarcuate element. The expandable elements can be biased to the expandedstate, e.g., by appropriate heat treating of the expandable elements.Alternatively, the expandable elements may be biased to the compressedstate.

In accordance with yet another aspect of the present invention, a clip,such as those described above, may be loaded on a delivery apparatus andused to close and/or seal an opening in a wall of a body lumen. Theapparatus generally includes a sheath including proximal and distal endsdefining a longitudinal axis there between. A housing is slidablydisposed on the sheath, the housing including an annular cavity therein.A clip, such as those described above, is disposed within the cavitywith the tissue engaging portions disposed substantially distally.

The housing can be actuable for advancing the clip distally towards thedistal end of the sheath, e.g., to deploy the clip from the cavity. Forexample, the apparatus may include an actuator coupled to the housing,the actuator configured for advancing the housing distally to deploy theclip. The actuator includes a spring mechanism for biasing the housingdistally upon activation of the actuator. In addition, the apparatus mayinclude a locator element for positioning the distal end of the sheath,such as a bleed back lumen or a mechanical locator.

During use, the distal end of the sheath, with the housing and clip nearits proximal end, may be positioned through a patient's skin along apassage and into a body lumen via an opening in the wall of the bodylumen. One or more instruments may be introduced through the lumen ofthe sheath into the body lumen. A diagnostic or therapeutic proceduremay be performed using the instruments at a location accessed via thebody lumen. For example, the body lumen is a peripheral blood vessel,such as a femoral artery, and the procedure may include angioplasty,atherectomy, stent delivery, delivery of a therapeutic agent, and/ortissue ablation.

The sheath may be manipulated, for example, with the aid of a locatorelement, to position the distal end with respect to the opening, e.g.,to ensure that the clip engages a wall of the body lumen or other tissueproximal to the opening and is not advanced into the body lumen itself.The housing is advanced distally into the passage, e.g., until thetissue engaging portions of the clip substantially engage the wall ofthe body lumen or other tissue proximal to the opening in the wall ofthe body lumen. In addition, or alternatively, the clip may be deployedfrom the housing, for example, by an ejector within the housing. Thesheath may then be withdrawn from the body lumen and passage, leavingthe clip in the passage. As the distal end of the sheath is withdrawnthrough the clip, the tissue engaging portions automatically at leastpartially move towards the planar configuration to pull the engagedtissue together and substantially close the opening.

In one embodiment, the clip automatically expands to an enlargedcross-section when the clip is deployed from the housing. Thus, the clipmay be compressed to facilitate loading into the housing, and therebyprovide a reduced profile for the clip. This may be useful to allow theclip to be delivered through a smaller puncture.

A method according to the present invention may include causing a clipor other closure element to engage tissue, e.g., muscle, fat, fascia,and the like, that is proximal to the body lumen. Thus, unlikepreviously known methods, which are directed to closing the wall of ablood vessel using clips or sutures, the present invention may includedeploying a closure element in the passage to cause it to engageintermediate tissue between the patient's skin and the wall of the bodylumen. When performed in this manner, the need to precisely position aclosure element may be avoided as is required when engaging the wall ofa vessel. Instead, the closure element may be located and delivered at arange of locations along the length of the passage yet still closeand/or seal the passage. In effect, extra-vascular tissue is engaged toclose the passage and thereby cause sealing of the wound. When theclosure element is deployed, it can be planar, e.g., extendingsubstantially parallel to the surface of the patient's skin, althoughnot necessarily so.

In one aspect of the present invention, a device for engaging tissueincludes a generally annular-shaped body defining a plane and disposedabout a central axis extending substantially normal to the plane. Thebody may be movable from a substantially planar configuration lyinggenerally in the plane towards a transverse configuration extending outof the plane. The body may also include a plurality of looped elementsincluding alternating first and second curved regions that define aninner and outer periphery of the body, respectively, in the planarconfiguration. A plurality of tines or other tissue-engaging elementsmay extend from the first curved regions, and may be oriented towardsthe central axis in the planar configuration, and substantially parallelto the central axis in the transverse configuration. The device may bebiased towards the planar configuration, e.g., to bias the tines towardsthe central axis.

The looped elements of the device may generally define an endless zigzagpattern, e.g., a sinusoidal pattern, extending about the central axis.The looped elements may facilitating deforming the device between theplanar and transverse configurations, e.g., by distributing stressesthrough the device and minimizing localized stresses in the curvedregions. In addition, the looped elements may be expandable betweenexpanded and compressed states for increasing and reducing a peripheryof the body in the transverse orientation, respectively. The loopedelements may be biased towards one of the compressed and expandedstates.

Adjacent tines of the device may have a first curved region disposedbetween them. The first curved region between adjacent tines may includea substantially blunt element extending towards the central axis. Theblunt element may have a length shorter than lengths of the adjacenttines.

In addition or alternatively, the tines of the device may include firstand second primary tines, having a first length and a second length,respectively, which may be the same as or different than one another.The first and second primary tines may be disposed on opposing firstcurved regions, and may be oriented substantially towards each other inthe planar configuration. In the planar configuration, the first andsecond primary tines may at least partially overlap. The tines may alsoinclude one or more secondary tines having a length substantiallyshorter than the first and second lengths of the primary tines. Thesecondary tines may be disposed on either side of the first and secondprimary tines.

In another aspect of the present invention, a device for engaging tissueincludes a generally annular-shaped body defining a plane and disposedabout a central axis extending substantially normal to the plane. Thebody may be movable from a substantially planar configuration lyinggenerally in the plane towards a transverse configuration extending outof the plane. A first primary tine, having a first length, may extendfrom the body towards the central axis in the planar configuration, andmay be deflectable out of the plane when the body is moved towards thetransverse configuration. A second primary tine, having a second length,may extend from the body towards the first tine when the body is in theplanar configuration, and may be deflectable out of the plane when thebody is moved towards the transverse configuration. The lengths of thefirst and second primary tines may cause the primary tines to at leastpartially overlap in the planar configuration. The body may be biasedtowards the planar configuration to bias the tines generally towards thecentral axis.

The device may include a set of secondary tines having a length shorterthan the first and second lengths. The secondary tines may extend fromthe body towards the central axis in the planar configuration, and maybe deflectable out of the plane when the body is moved towards thetransverse configuration. In an exemplary embodiment, a secondary tinemay be disposed on either side of the first primary tine, and asecondary tine may be disposed on either side of the second primarytine.

Optionally, adjacent tines may have a first curved region disposedbetween them. The first curved region between adjacent tines may includea substantially blunt element extending towards the central axis. Theblunt element may have a length shorter than lengths of the adjacenttines.

Also, the device may include a plurality of looped elements disposedaround a periphery of the body. The looped elements may generally definean endless zigzag pattern extending about the central axis. The firstprimary tine and the second primary tine may extend from looped elementsdisposed opposite one another. The looped elements may be expandablebetween expanded and compressed states for increasing and reducing aperiphery of the body in the transverse orientation, respectively. Thelooped elements may be biased towards one of the compressed and expandedstates.

In another aspect of the present invention, a method is provided formanufacturing a clip from an elastic material, such as a sheet ofsuperelastic alloy, e.g., a nickel-titanium alloy (“Nitinol”). Thecomponents of the clip, e.g., a generally-annular body, optionallyincluding looped elements, and/or tines, may be formed by removingportions from the sheet. The portions may be removed, e.g., by lasercutting, chemical etching, photo chemical etching, stamping, electricaldischarge machining, and the like. The clip may be polished using one ormore processes, such as electro-polishing, chemical etching, tumbling,sandblasting, sanding, and the like, and/or heat-treated to provide adesired finish and/or desired mechanical properties. Optionally, thebody and tines may be coated with a therapeutic agent, e.g., a peptidecoating and/or one or more clotting factors.

In addition or alternatively, the clip may be disposed in a planarconfiguration, e.g., upon forming the clip from the sheet, and heattreated to form a clip biased to the planar configuration. For example,the clip may be formed from a shape memory material, e.g., Nitinol,which may substantially recover the planar configuration when heated toa first predetermined temperature corresponding to an austenitic state,e.g., a temperature close to body temperature. The clip may be cooled toa second predetermined temperature corresponding to a martensitic state,e.g., a temperature at or below ambient temperature, and malleablymanipulated. For example, the clip formed from the sheet may be deformedto a transverse configuration, such as that described above, e.g., byloading the clip onto a mandrel or directly onto a delivery device. Ifthe clip includes looped elements formed from the body, the loopedelements may be biased upon heat treatment towards an expanded state,but may be malleably deformed to a compressed state upon cooling, e.g.,to facilitate loading onto the delivery device. Alternatively, the clipmay be formed from a superelastic material, e.g., Nitinol, such that theclip may be resiliently deformed to the transverse configuration and/orcompressed state, yet may automatically attempt to resume its planarconfiguration and/or expanded state upon release from external forces.

In still another aspect of the present invention, a method for closingan opening in a wall of a body lumen is provided. The distal end of anelongate member may be advanced through an opening in a patient's skin,along a passage through tissue, and into the body lumen. A distalportion of an obturator may be positioned distally beyond the distal endof the elongate member along the passage within the body lumen. One ormore expandable elements on the distal portion of the obturator may beexpanded transversely. The obturator may be withdrawn from the passageuntil the expandable elements contact the wall of the body lumen,thereby providing a tactile indication of a location of the wall of thebody lumen between the elongate member and the plurality of expandableelements of the obturator.

A clip may be advanced into the passage over the elongate member untiltines of the clip penetrate the wall of the body lumen, the tines andthe expandable elements on the obturator being angularly offset from oneanother such that the tines penetrate the wall at locations between theexpandable elements. The obturator may be collapsed, and the elongatemember and/or obturator may be withdrawn from the body lumen andpassage, leaving the clip to substantially close the opening in the wallof the body lumen. When the elongate member is withdrawn, the tines mayautomatically at least partially move towards a planar configuration tosubstantially close the opening.

The tines of the clip may include primary tines and secondary tines.Here, advancing the clip may include puncturing the wall of the bodylumen with the primary tines until tips of the primary tines enter thebody lumen, and puncturing the wall of the body lumen with the secondarytines. The primary tines and the secondary tines may puncture the wallswithout contacting the expandable elements of the obturator.

The present invention is also directed to methods for manufacturingtissue engaging clips in a manner in which a clip-precursor is firstformed and such precursor is then reconfigured into the final shape ofthe clip. In one embodiment of the invention, a clip having an annularor hoop-shaped generally planar configuration with radially inwardlyextending tines is manufactured by first forming a precursor with thetines extending radially outward and then reconfigured by inserting theprecursor to its final shape with the tines extending radially inwardand then heat setting the clip in this configuration. This permits thetines to be packed more closely together which enhances the sealingfunction of the clip and reduces the size of the clip's footprint. Aswill be explained in more detail herein, this manufacturing methodovercomes the limitations of conventional methods in which the clip ismanufactured in its final configuration.

In another embodiment, an annular or hoop-shaped planar clip precursorwith radially inwardly extending tines is first manufactured in anoversize configuration and then has its lateral dimensions reduced topack the tines closer together and to reduce the footprint of the clipand then heat set in that configuration.

The present invention is directed to vascular closure devices or clipshaving a design particularly suitable for closing a puncture in a wallof a blood vessel formed during a diagnostic or therapeutic procedure.According to the present invention, a device for engaging tissueincludes a generally annular-shaped body defining a plane and disposedabout a central axis extending substantially normal to the plane. Thebody may be movable from a substantially planar configuration lyinggenerally in the plane towards a transverse configuration extending outof the plane. The body also includes a plurality of looped elementsincluding alternating first and second curved regions that define aninner and outer periphery of the body, respectively, in the planarconfiguration. A plurality of tines or other tissue-engaging elementsextend from the first curved regions, and are oriented towards thecentral axis in the planar configuration, and substantially parallel tothe central axis in the transverse configuration. The device may bebiased towards the planar configuration, e.g., to bias the tines towardsthe central axis.

The looped elements of the device may generally define an endless zigzagpattern, e.g., a sinusoidal pattern, extending about the central axis.The looped elements may facilitating deforming the device between theplanar and transverse configurations, e.g., by distributing stressesthrough the device and minimizing localized stresses in the curvedregions. In addition, the looped elements may be expandable betweenexpanded and compressed states for increasing and reducing a peripheryof the body in the transverse orientation, respectively. The loopedelements may be biased towards one of the compressed and expandedstates.

Adjacent tines of the device may have a first curved region disposedbetween them. The first curved region between adjacent tines may includea substantially blunt element extending towards the central axis. Theblunt element may have a length shorter than lengths of the adjacenttines.

The tines of the device may include first and second primary tines,having a first length and a second length, respectively, which may bethe same as or different than one another. The first and second primarytines may be disposed on opposing first curved regions, and may beoriented substantially towards each other in the planar configuration.In the planar configuration, the first and second primary tines may atleast partially overlap the body or each other. The tines may alsoinclude one or more secondary tines having a length substantiallyshorter than the first and second lengths of the primary tines. Thesecondary tines may be disposed on either side of the first and secondprimary tines.

A first primary tine, having a first length, may extend from the bodytowards the central axis in the planar configuration, and may bedeflectable out of the plane when the body is moved towards thetransverse configuration. A second primary tine, having a second length,may extend from the body towards the first tine when the body is in theplanar configuration, and may be deflectable out of the plane when thebody is moved towards the transverse configuration. The lengths of thefirst and second primary tines may cause the primary tines to at leastpartially overlap in the planar configuration. The body may be biasedtowards the planar configuration to bias the tines generally towards thecentral axis.

The device may include a set of secondary tines having a length shorterthan the first and second lengths. The secondary tines may extend fromthe body towards the central axis in the planar configuration, and maybe deflectable out of the plane when the body is moved towards thetransverse configuration. In an exemplary embodiment, a secondary tinemay be disposed on either side of the first primary tine, and asecondary tine may be disposed on either side of the second primarytine.

Optionally, adjacent tines may have a first curved region disposedbetween them. The first curved region between adjacent tines may includea substantially blunt element extending towards the central axis. Theblunt element may have a length shorter than lengths of the adjacenttines.

Also, the device may include a plurality of looped elements disposedaround a periphery of the body. The looped elements may generally definean endless zigzag pattern extending about the central axis. The firstprimary tine and the second primary tine may extend from looped elementsdisposed opposite one another. The looped elements may be expandablebetween expanded and compressed states for increasing and reducing aperiphery of the body in the transverse orientation, respectively. Thelooped elements may be biased towards one of the compressed and expandedstates.

In any event, the primary tines of the clips of the present inventionwill be offset from the axis of symmetry of the loop from which theyextend. The offsetting of the primary tines is achieved by simplyrelocating the primary tines which are directly attached to the loop toa location which is not on the axis of symmetry of the loop or providingan intermediate connecting element between the tines and the axis ofsymmetry of the curved region of the loop from which the tine extends.This connecting element is straight or linear, but may also be curved.The connecting element can be connected to a point or region on the axisof symmetry of the loop to enhance consistency of performance of theclip during deployment. The offsetting of the tines is believed toreduce any tendency to wander during deployment, which the tines mightotherwise have.

In another aspect of the present invention, a method is provided formanufacturing a clip from an elastic material, such as a sheet ofsuperelastic alloy, e.g., a nickel-titanium alloy (“Nitinol”). Thecomponents of the clip, e.g., a generally-annular body, optionallyincluding looped elements, and/or tines, may be formed by removingportions from the sheet. The portions may be removed, e.g., by lasercutting, chemical etching, photo chemical etching, stamping, electricaldischarge machining, and the like, or by the method disclosed in one ormore of the incorporated by reference patents or patent applications.The clip may be polished using one or more processes, such aselectro-polishing, chemical etching, tumbling, sandblasting, sanding,and the like, and/or heat-treated to provide a desired finish and/ordesired mechanical properties. Optionally, the body and tines may becoated with a therapeutic agent, e.g., a peptide coating and/or one ormore clotting factors.

In addition or alternatively, the clip may be disposed in a planarconfiguration, e.g., upon forming the clip from the sheet, and heattreated to form a clip biased to the planar configuration. For example,the clip may be formed from a shape memory material, e.g., Nitinol,which may substantially recover the planar configuration when heated toa first predetermined temperature corresponding to an austenitic state,e.g., a temperature close to body temperature. The clip may be cooled toa second predetermined temperature corresponding to a martensitic state,e.g., a temperature at or below ambient temperature, and malleablymanipulated.

For example, the clip formed from the sheet may be deformed to atransverse configuration, such as that described above, e.g., by loadingthe clip onto a mandrel or directly onto a delivery device. If the clipincludes looped elements formed from the body, the looped elements maybe biased upon heat treatment towards an expanded state, but may bemalleably deformed to a compressed state upon cooling, e.g., tofacilitate loading onto the delivery device. Alternatively, the clip maybe formed from a superelastic material, e.g., Nitinol, such that theclip may be resiliently deformed to the transverse configuration and/orcompressed state, yet may automatically attempt to resume its planarconfiguration and/or expanded state upon release from external forces.

In still another aspect of the present invention, a method for closingan opening in a wall of a body lumen is provided. The distal end of anelongate member may be advanced through an opening in a patient's skin,along a passage through tissue, and into the body lumen. A distalportion of an obturator may be positioned distally beyond the distal endof the elongate member along the passage within the body lumen. One ormore expandable elements on the distal portion of the obturator may beexpanded transversely. The obturator may be withdrawn from the passageuntil the expandable elements contact the wall of the body lumen,thereby providing a tactile indication of a location of the wall of thebody lumen between the elongate member and the plurality of expandableelements of the obturator.

A clip may be advanced into the passage over the elongate member untiltines of the clip penetrate the wall of the body lumen, the tines andthe expandable elements on the obturator being angularly offset from oneanother such that the tines penetrate the wall at locations between theexpandable elements. The obturator may be collapsed, and the elongatemember and/or obturator may be withdrawn from the body lumen andpassage, leaving the clip to substantially close the opening in the wallof the body lumen. When the elongate member is withdrawn, the tines mayautomatically at least partially move towards a planar configuration tosubstantially close the opening. The clip may also be delivered to thedesired site by using the apparatus and methods disclosed in U.S. patentapplication Ser. No. 10/356,214, filed Jan. 30, 2003 and Ser. No.10/638,115, filed Aug. 8, 2003. The clip may also be manufacturedaccording to the method set forth in U.S. patent application Ser. No.10/335,075, filed Dec. 31, 2002.

Advancing the clip may include puncturing the wall of the body lumenwith the primary tines until tips of the primary tines enter the bodylumen, and puncturing the wall of the body lumen with the secondarytines. The primary tines and the secondary tines may puncture the wallswithout contacting the expandable elements of the obturator.

The present invention also relates to a method for closing an opening ina wall of a body lumen. The method can include advancing a distal end ofan elongate member within the body lumen, the elongate member having adistal portion that assists in presenting the wall for receiving a cliphaving a plurality of tissue engaging portions having tips that pointgenerally toward a central axis of the clip. Further, the method caninclude advancing the clip relative to the elongate member and the wallof the body lumen until the plurality of tissue engaging portionspenetrate the wall of the body lumen. Optionally, the clip can beadvanced until a distal end of the plurality of tissue engagementportions penetrate the wall but do not enter the body lumen. Statedanother way, the method can include stopping advancement of the clipbefore the distal end of the plurality of tissue engagement portionsenter the body lumen. Once the clip penetrates the wall, the elongatemember can be withdrawn from the body lumen, leaving the clip tosubstantially close the opening in the wall of the body lumen.

According to another aspect, the method can include advancing a secondelongate member relative to the elongate member, the clip slidablycooperating with the second elongate member. Withdrawing the secondelongate member relative to the elongate member following penetration ofthe plurality of tissue engaging portions into the wall of the bodylumen can enable the plurality of tissue engaging portions toautomatically at least partially move towards a planar configuration tosubstantially close the opening.

The method can also related to closing a opening in a wall of a bodylumen by (i) advancing a distal end of a first elongate member withinthe body lumen, the elongate member having a distal portion that assistsin presenting the wall for receiving a clip having a plurality of tissueengaging portions symmetrically disposed about the clip, (ii) advancingthe clip relative to the elongate member and the wall of the body lumen,as the distal portion of the elongate member assists with presenting thewall for receiving the clip, until the plurality of tissue engagingportions penetrate the wall of the body lumen, the tissue engagingportions and the distal portion of the elongate member being angularlyoffset from one another; and (iii) withdrawing the elongate member fromthe body lumen, leaving the clip to substantially close the opening inthe wall of the body lumen.

To aid with positioning the clip relative to the wall, the method canfurther include positioning the distal portion of the first elongatemember relative to the wall to assist in presenting the wall forreceiving the clip to close the opening. In addition, the method caninclude moving the clip within a carrier assembly that moves relative toa second elongate member, toward the distal portion of the firstelongate member until the clip deploys from within the carrier assembly.

Still another method of closing an opening in a wall of a body lumen caninclude advancing a distal end of a first elongate member within thebody lumen, the elongate member having a distal portion that assists inpresenting the wall for receiving a clip having a plurality of tissueengaging portions symmetrically disposed about the clip. The method canfurther include positioning a distal end of a second elongate memberrelative to the first elongate member, the second elongate member havinga carrier assembly that receives the clip, and advancing the cliprelative to the wall of the body lumen, as the distal portion of thefirst elongate member assists with presenting the wall for receiving theclip, until the plurality of tissue engaging portions penetrate the wallof the body lumen. Once the clip penetrates the wall, the method caninclude withdrawing the first elongate member and the second elongatemember from the body lumen, leaving the clip to substantially close theopening in the wall of the body lumen.

These and other objects and features of the present invention willbecome more fully apparent from the following description and appendedclaims, or may be learned by the practice of the invention as set forthhereinafter.

BRIEF DESCRIPTION OF THE DRAWINGS

To further clarify the above and other advantages and features of thepresent invention, a more particular description of the invention willbe rendered by reference to specific embodiments thereof which areillustrated in the appended drawings. It is appreciated that thesedrawings depict only typical embodiments of the invention and aretherefore not to be considered limiting of its scope. The invention willbe described and explained with additional specificity and detailthrough the use of the accompanying drawings in which:

FIG. 1A illustrates a top view of a first embodiment of a clip includinga plurality of tissue engaging portions in a planar orientation, inaccordance with the present invention.

FIGS. 1B and 1C illustrate side views of the clip of FIG. 1A, with thetissue engaging portions oriented substantially transversely from theplanar orientation, in reduced and expanded diameters, respectively.

FIG. 1D illustrates a top view of the clip of FIG. 1A with the tinesoriented substantially transversely from the planar orientation.

FIG. 2 illustrates a top view of another embodiment of a clip, inaccordance with the present invention.

FIG. 3 illustrates a top view of another embodiment of a clip, inaccordance with the present invention.

FIG. 4 illustrates a top view of another embodiment of a clip, inaccordance with the present invention.

FIG. 5 illustrates a top view of another embodiment of a clip, inaccordance with the present invention.

FIG. 6 illustrates a top view of the clip of FIG. 5 with the clipunwound from its annular shape.

FIGS. 7A and 7B illustrate top views of an alternative embodiment of theclip of FIG. 5, the clip shown unwound and including expandable elementsshown in their expanded and compressed states, respectively.

FIGS. 8A and 8B illustrate top views of another alternative embodimentof the clip of FIG. 5, the clip shown unwound and including expandablecells shown in their expanded and compressed states, respectively.

FIG. 9 illustrates a side view of an apparatus for delivering a clip,including an introducer sheath and an actuator assembly, in accordancewith the present invention.

FIGS. 10A-10D illustrates cross-sectional views of a blood vessel,showing a method for delivering a closure device into a passagecommunicating with the vessel such that the closure device engages thevessel wall.

FIGS. 11A-11D illustrate cross-sectional views of a blood vessel,showing another method for delivering a closure device into a passagecommunicating with the vessel such that the closure device engagesextra-vascular tissue proximal to the vessel wall.

FIG. 12 illustrates a top view of an alternative embodiment of a clip,in accordance with the present invention.

FIGS. 13-15 illustrate top views of additional embodiments of a clip, inaccordance with the present invention.

FIG. 16A illustrates a top view of another embodiment of a clipincluding a plurality of tines in a planar orientation, in accordancewith the present invention.

FIGS. 16B and 16C illustrate side views of the clip of FIG. 16A, withthe tines oriented substantially transversely from the planarorientation, in compressed and expanded states, respectively.

FIG. 17A illustrates a top view of yet another embodiment of a clipincluding a plurality of tines in a planar orientation, in accordancewith the present invention.

FIGS. 17B and 17C illustrate side views of the clip of FIG. 17A, withthe tines oriented substantially transversely from the planarorientation, in compressed and expanded states, respectively.

FIG. 18 illustrates a top view of another embodiment of a clip, inaccordance with the present invention.

FIG. 19 illustrates a top view of an embodiment of a clip havingradiopaque markers thereon.

FIG. 20 illustrates a top view of an embodiment of a clip having pocketsfor holding radiopaque markers therein.

FIG. 21 illustrates a top view of another embodiment of a clip includingstop elements, in accordance with the present invention.

FIG. 22 illustrates a top view of yet another embodiment of a clipincluding stop elements, in accordance with the present invention.

FIG. 23 illustrates a top view of still another embodiment of a clipincluding stop elements, in accordance with the present invention.

FIG. 24 illustrates a side view of an apparatus, including an introducersheath and an obturator, suitable for delivering a clip of the presentinvention.

FIGS. 25A-25D illustrate cross-sectional views of a blood vessel,showing a method for delivering a clip into a passage communicating withthe vessel using the apparatus of FIG. 24.

FIG. 26A illustrates a top view of the blood vessel of FIGS. 25A-25D,showing the orientation of the expandable elements of the obturator andopenings produced by primary tines of the clip relative to anarteriotomy in the vessel.

FIG. 26B illustrates Figure a top view of the blood vessel of FIG. 26A,showing the arteriotomy being closed by the clip.

FIG. 27 illustrates a top view of an embodiment of a clip having arcuatetines, in accordance with the present invention.

FIGS. 28A and 28B illustrate the before and after configuration of aclip manufactured according to one embodiment of this invention.

FIGS. 29A and 29B illustrate the before and after-configuration of aclip manufactured according to another embodiment of the invention.

FIGS. 30A-30C illustrate alternate before and after-configurations ofclips manufactured according to the method of this invention.

FIG. 31 illustrates a clip which, while generally planar, has tineswhich extend radially inwardly at an angle to the plane defined by thebody.

FIGS. 32 and 33 illustrate clip precursors in which radially opposedprimary tines have different lengths.

FIG. 34 illustrates one relationship between the grain orientation of aNitinol sheet and the primary tines of a clip precursor.

FIG. 35A illustrates a top view of a clip including a plurality of tinesin a planar orientation, in which the primary tines are offset from theaxis of symmetry of the loop from which they extend and are connected toa curved region of the loop by a straight connecting element inaccordance with the present invention.

FIGS. 35B and 35C illustrate side views of the clip of FIG. 35A, withthe tines oriented substantially transversely from the planarorientation, in compressed and expanded states, respectively.

FIG. 36 illustrates a clip according to the present invention in whichthe primary tines overlap with the body of the clip.

FIGS. 37A-37C illustrates top views of clips in which the primary tinesare offset from the axis of symmetry of the loop from which they extendby a connecting element which is at least partially curved.

FIG. 38 illustrates a clip in which the primary tines have differentlengths.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention is directed to devices and methods for engagingtissue, e.g., to connect tissue segments together or to close and/orseal openings through tissue, such as in a wall of a body lumen. Moreparticularly, the present invention is directed to vascular closuredevices or clips for closing a puncture in a wall of a blood vesselformed during a diagnostic or therapeutic procedure, and to methods formaking and using such devices.

Turning now to the drawings, FIGS. 1A-1D show a first embodiment of aclosure device or clip 10 for closing an incision, puncture, or otherpassage communicating with a blood vessel or other body lumen (notshown). The clip 10 includes a peripheral body 12 and a plurality oftissue engaging portions 14. Each tissue engaging portion 14 includes apair of legs 16 terminating in a tine 18 configured for penetrating orotherwise engaging tissue. The tines 18 may include a variety of knownpointed tips, such as a bayonet tip, and/or may include barbs (notshown) along an edge or planar surface of the tine 18. The tissueengaging portions 14 are disposed substantially symmetrically about acentral axis 24. The body 12 also can include a plurality of expandablecells 20 that are connected by hinged regions 22 that also connectadjacent tissue engaging portions 14.

In another embodiment, the body 12 and tissue engaging portions 14 areintegrally formed from a single sheet of material, such as asuperelastic alloy, such as a nickel-titanium (“Nitinol”) alloy.Portions of the sheet may be removed using conventional methods, such aslaser cutting, chemical etching, and the like, to form the clip 10. FIG.1A shows the clip 10 with the tissue engaging portions 14 in asubstantially planar configuration lying in a plane defined by thesheet. The clip 10 may include one or more radiopaque markers or othermarkers visible using external imaging, such as fluoroscopy. Forexample, the entire clip 10 may be coated with radiopaque material, orone or more discrete markers may be provided at predetermined locationson the clip 10.

As shown in FIGS. 1B and 1D, the tissue engaging portions 14 may bedeflected such that they extend from the body 12 substantiallytransversely with respect the plane defined by the sheet. The tissueengaging portions 14 can be oriented substantially parallel to the axis24 to define a transverse configuration, as shown in FIG. 1B.Alternatively, the tissue engaging portions 14 may define an angle withrespect to the axis 24, as shown in FIG. 1D. In the clip's transverseconfiguration, the body 12 has a generally annular shape, e.g., ahexagonal shape as shown in FIG. 1D. The body 12 is sufficientlyflexible such that the clip 10 assumes a generally circular orelliptical shape (not shown), e.g., conforming to an exterior surface ofa delivery device (not shown) used to delivery the clip 10.

The tissue engaging portions 14 can be biased from the transverseconfiguration towards one another, i.e., towards the planarconfiguration of FIG. 1A. Thus, with the tissue engaging portions 14 inthe transverse configuration, the tines 18 may be engaged with tissue,e.g. adjacent to a puncture site. When the clip 10 is released, thetissue engage portions 14 may attempt to return to the planarconfiguration, thereby drawing the engaged tissue together andsubstantially closing and/or sealing the puncture site.

In addition, the expandable cells 20 may be expandable from a compressedstate, shown in FIG. 1B, to an expanded state, shown in FIG. 1C. Theexpandable cells 20 can be biased to the expanded state, but may becompressed to the compressed state, e.g., by constraining the clip 10.In one embodiment, the clip 10 is formed with the expandable cells 20 inthe expanded state. With the clip in its transverse configuration, theexpandable cells 20 may be circumferentially and/or radially compressedto the compressed state such that the clip 10 defines a first diameter26 a, shown in FIG. 1B. The clip 10 may be constrained at the firstdiameter, e.g., by loading the clip 10 into a delivery device (notshown), as described further below. When released from the constraint,e.g., when deployed from the delivery device, the clip 10 mayautomatically expand to a second diameter 26 b, shown in FIG. 1C. Thus,the expandable cells 20 may reduce the profile of the clip 10 duringdelivery, e.g., to facilitate introduction of the clip 10 through asmaller puncture or other passage.

In an alternative embodiment, the clip 10 may be formed from a shapememory alloy, e.g., Nitinol, with the expandable cells in the compressedstate. With the clip 10 in the transverse configuration, the clip 10 maybe expanded, e.g., by applying a force radially outwards against aninner surface of the clip 10, thereby expanding the expandable cells 20to the expanded state and expanding the clip 10 to the second diameter26 b. The expandable cells 20 may then be heat treated to cause theexpandable cells 20 to “remember” the expanded state, as is known tothose skilled in the art. It may also be necessary to subsequently heattreat the clip 10 further, e.g. with the tissue engaging portions 14 inthe planar configuration to cause the tissue engaging portions 14 to“remember” and be biased to the planar configuration, as is known tothose skilled in the art.

Turning to FIG. 2, another embodiment of a clip 110 is shown thatincludes a peripheral body 112 and a plurality of tissue engagingportions 114. Each tissue engaging portion 114 includes a pair of legs116 terminating in a tine 118. The tissue engaging portions 114 aredisposed substantially symmetrically about a central axis 124. The body112 also can include a plurality of expandable cells 120 that areconnected by hinged regions 122 that also connect adjacent tissueengaging portions 114, similar to the first embodiment described above.

The tissue engaging portions 114 may be deflected such that they extendsubstantially transversely from the body 112 (not shown). The tissueengaging portions 114 may be oriented substantially parallel to the axis124 to define a transverse configuration such that the body 112 has agenerally annular shape. The tissue engaging portions 114 can be biasedfrom the transverse configuration towards one another, i.e., towards theplanar configuration of FIG. 2, similar to the previous embodiment.

The expandable cells 120 have a generally arcuate shape that may beexpandable from a first width to a second wider width (not shown),behaving similarly to the diamond-shaped cells of the previousembodiment. Thus, the expandable cells 120 may be biased to the expandedstate, but may be compressed to the compressed state, as describedabove.

Turning to FIG. 3, another embodiment of a clip 210 is shown thatincludes a peripheral body 212 including a plurality of arms 216extending between tissue engaging portions or tines 214; expandablecells 220, and hinged regions 222. The clip 210 can be formed from asingle sheet of material, similar to the embodiments described above,with the tines 214 biased to a planar configuration, as shown. The body212 is deflectable to a transverse configuration (not shown) such thatthe tines 212 are oriented substantially transversely with respect tothe plane of the sheet. The body 212, and particularly the arms 216, aresufficiently flexible such that the clip 210 may assume a generallyannular shape in the transverse configuration, e.g., to facilitateloading of the clip 210 onto a delivery device (not shown).

The expandable cells 220 are substantially enclosed loops that may atleast partially open from a compressed state (shown in FIG. 2), to anexpanded state (not shown). The loops can be biased to the expandedstate, similar to the embodiments described above, thereby allowing theclip 210 to assume a reduced diameter and an expanded diameter.

Turning to FIG. 4, another embodiment of a clip 310 is shown, that issimilar to the embodiment shown in FIG. 3, except that the clip 310includes only two expandable cells 320. The expandable cells 320 arestill disposed in a substantially symmetrical arrangement to facilitateexpansion of the clip 310 in a generally uniform manner. As will beappreciated by those skilled in the art, a clip in accordance with thepresent invention may have a variety of configurations, including two ormore tissue engaging portions or tines, and including one or moreexpandable cells (or optionally no expandable cells). The tissueengaging portions and/or expandable cells can be arranged in asubstantially symmetrical configuration, for example, about a centralaxis.

Turning to FIG. 5, another embodiment of a clip 410 is shown thatincludes a peripheral body 412 and a plurality of tissue engagingportions 414 terminating in tines 418. The clip 410 may be formed from asingle sheet of material, such as Nitinol, similar to the embodimentsdescribed above.

Alternatively, as shown in FIG. 6, the clip 410 may be formed from anelongate wire 430, e.g., a solid rod or hollow tube, such as a length ofhypotube. The tube 430 can be semi-rigid or flexible, therebyaccommodating deflection of the clip 410 between its planar andtransverse configurations, as described further below. The tube 430 maybe bent and tines 418 may be formed therein using conventional methods.Alternatively, tines 418 may be formed separately and attached to thetube 430, for example, by welding. The tube 430 may then be wound intoan enclosed loop and the ends 432, 434 may be connected together, e.g.,by welding, to provide a clip 410, such as that shown in FIG. 5.

In this embodiment, the tissue engaging regions 414 are disposed inopposing sets along an axis of symmetry 424 extending between loopedregions 426, defining a substantially planar configuration. The tissueengaging portions 414 may be directed substantially transversely withrespect to a plane defined by the planar configuration, but can bebiased to return towards the planar configuration, similar to theembodiments described above.

In an alternative embodiment, shown in FIGS. 7A and 7B, the regions 426′between the tissue engaging portions 414 include expandable elements420, having a zig-zag shape, that are expandable between a compressedstate and an expanded state. Thus, when the tube 412′ is wound to form aclip (not shown), the zig-zag elements 420 are disposed at the loopedregions 426′ of the clip. The zig-zag elements 420 have a first width w₂in the compressed state (FIG. 7B) and a second width w₂ in the expandedstate that is larger than the first width (FIG. 7A). In a furtheralternative embodiment, shown in FIGS. 8A and 8B, the expandableelements are substantially enclosed cells 420′, optionally having adiamond shape. Thus, similar to the embodiments described above, theexpandable elements or cells allow the clip 410″ to assume first andsecond diameters.

Turning to FIG. 9, an apparatus 50 is shown that may be used to delivera clip, such as any of the embodiments described above. Generally, theapparatus 50 includes an introducer sheath 52, and a housing 54 slidablydisposed on the sheath 52. The sheath 52 includes a substantiallyflexible or semi-rigid tubular body 58 including a lumen 60 extendingbetween its proximal and distal ends 62, 64. The distal end 64 has asize and shape to facilitate insertion into a blood vessel, e.g., havinga tapered tip for facilitating substantially atraumatic introductionthrough the passage and at least partially into the vessel. The lumen 60has a size for accommodating insertion of one or more devicestherethrough, such as a catheter, guidewire, and the like (not shown).The sheath 52 also can include a seal (not shown), such as a hemostaticvalve, within the lumen 60 at or near the proximal end 62 that providesa fluid-tight seal, yet accommodates insertion of one or more devicesinto the lumen 60 without fluid passing proximally from the sheath 52.

Optionally, the sheath 52 may include a side port 66 that communicateswith the lumen 60, for example, to allow the infusion of fluids into thelumen 60, through the sheath 52. Alternatively, or in addition, the sideport 66 may be used to provide a “bleed back” indicator, such as thatdisclosed in U.S. Pat. No. 6,626,918, entitled “Apparatus and Methodsfor Positioning a Vascular Sheath,” which is assigned to the assignee ofthe present invention, and the disclosures of which, and any referencestherein, are incorporated herein in their entirety by this reference.Alternatively, the apparatus 50 may include a mechanical locator (notshown), such as that disclosed in U.S. Pat. No. 6,780,197, filed on thesame day with U.S. Pat. No. 6,719,777, entitled “Apparatus and Methodfor Delivering a Closure Device,” the disclosures of which, and anyreferences therein, are incorporated herein in their entirety by thisreference.

The housing 54 is slidably disposed on an exterior of the sheath 52, thehousing 54 configured for releasably holding the clip 10, e.g., withinan annular cavity therein (not shown). The housing may be substantiallypermanently attached to the sheath 52 or, alternatively, the housing 54may be attachable to the sheath 52, e.g., using an outer sleeve (notshown). This outer sleeve may have the housing thereon, and the sleevemay be advanced over the sheath 52, and coupled thereto at any timeduring its use. Exemplary embodiments of a housing for use with anapparatus in accordance with the present invention are disclosed in U.S.Pat. Nos. 6,197,042, 6,461,364, and 6,391,048, the disclosures of which,and any references therein, are incorporated herein in their entirety bythis reference.

The housing 54 is actuable from the proximal end 62 of the sheath 52,for example, by a housing actuator assembly (not shown), for advancingthe clip 10 distally during deployment. A rod, cable, or other controlwire (not shown) may couple the housing 54 to the actuator assembly. Thehousing actuator assembly may be detachable from the sheath 52, e.g., tofacilitate introduction of devices into the lumen 60. In one embodiment,the actuator may be biased to advance the housing 54 upon activation.Thus, when activated, the housing 54 may be advanced towards the distalend of the sheath 52 to deploy the clip 10.

Turning to FIGS. 10A-10D, the apparatus 50 may be used to deliver a clip10, e.g., to close and/or seal an incision, puncture, or other passage92 that extends from a patient's skin 94 through intervening tissue 96,and a wall 98 of the vessel 90. Alternatively, the apparatus 50 may beused to deliver any of the clips disclosed herein to engage tissue inother procedures, e.g., to connect tissue segments together or otherwiseto secure tissue structures engaged by the clip with respect to oneanother. For example, the apparatus and clip may be used to attach ananastomosis during a bypass procedure. It will be appreciated by thoseskilled in the art that a clip and/or apparatus in accordance with thepresent application may be useful in a variety of procedures, includingtubal ligations, and the like.

Generally, the clip 10 is pre-loaded in the housing 54 before theprocedure. The clip 10 may be constrained in its substantiallytransverse configuration and then introduced over the distal end 64 ofthe sheath 52 and into the cavity or otherwise loaded in the housing 54.Because the tissue engaging portions (not shown) of the clip 10 arebiased to a planar configuration, they may engage an inner wall (notshown) of the housing 54 or an outer surface of the sheath 52, therebyconstraining the clip 10 in its transverse configuration. Alternatively,the clip 10 may be directed over the distal end 64 of the sheath 62,thereby causing the tissue engaging portions to deflect transverselyfrom the planar configuration towards a substantially axial or distalconfiguration.

As shown in FIG. 10A, the sheath 52 may be inserted or otherwisepositioned within the blood vessel 90, i.e., through the passage 92. Thesheath 52 can be provided with the housing 54 in its proximal position,e.g., without the housing actuator assembly (not shown) attached.Alternatively, the housing actuator assembly may be provided attached tothe sheath 52 as long as the lumen 60 may be accessed. In a furtheralternative, the housing 54 may be provided separately from the sheath62 with the clip 10 preloaded therein. For example, the housing 54 maybe provided on an elongate member, such as a tubular or U-shaped sleeve(not shown), that may be advanced over and coupled to the sheath 52 atany time before deployment of the clip 10. The housing actuator may becoupled to the sleeve and/or may be attachable to the sleeve.

The sheath 52 may be advanced over a guidewire or other rail (not shown)previously positioned through the passage 92 into the blood vessel 90using a conventional procedure. The blood vessel 90 can be a peripheralvessel, such as a femoral, radial, or carotid artery, although otherbody lumens may be accessed using the sheath 52, as will be appreciatedby those skilled in the art.

The passage 92, and consequently the sheath 52, may be oriented at asubstantially acute angle “alpha” with respect to the vessel 90, therebyfacilitating introduction of devices through the lumen 60 of the sheath52 into the vessel 90 with minimal risk of damage to the vessel 90. Oneor more devices, such as a guide wire, a catheter, and the like (notshown), may be inserted through the sheath 52 and advanced to a desiredlocation within the patient's body. For example, the devices may be usedto perform a therapeutic or diagnostic procedure, such as angioplasty,atherectomy, stent implantation, and the like, within the patient'svasculature.

After the procedure is complete, the device(s) may be removed from thesheath 52. The sheath 52 may be manipulated to position the distal end64 with respect to the opening 92, e.g., to ensure that the housing 54is advanced to properly deploy the clip 10 in the wall 98 of the vessel90. Bleed back or mechanical locators may be used to facilitate thispositioning.

As shown in FIG. 10B, with the sheath 52 properly positioned, thehousing 54 may be actuated, for example, to advance the housing 54distally into the passage 92 to deliver the clip 10. Movement of thehousing 54 with respect to the distal end 64 of the sheath 52 can belimited, e.g., by the actuator assembly. Thus, the housing 54 may onlybe advanced a fixed distance such that the clip 10 substantially engagesthe wall 98 of the blood vessel 90, e.g., until the tines 18 penetratebut do not pass completely through the wall 98. Once the clip 10 issuccessfully deployed within the passage 92, i.e., into the wall 98 ofthe vessel 90, the apparatus 50 may be withdrawn from the passage 92.

In addition, as the clip 10 is deployed from the housing 54, the clip 10may expand radially to an enlarged diameter (not shown), for example, ifthe clip 10 includes expandable elements (not shown), such as thosedescribed above. Thus, the clip 10 may be compressed into the housing54, e.g., thereby allowing a smaller profile housing 54 to be used. Theclip 10 may be expanded upon deployment to engage a larger area oftissue adjacent the opening in the wall 98 of the vessel 90.

As shown in FIG. 10C, as the distal end 64 of the sheath 52 is withdrawnproximally from around the clip 10, the tines 18 of the clip 10 are freeto return towards the planar configuration. Thus, the tines 18 beginautomatically to move from a substantially axial configuration to a lesstransverse configuration. Because the tines 18 are engaged to thetissue, however, they may not return completely to the planarconfiguration. Because of the bias to the planar configuration, however,the tines 18 automatically pull the tissue together, thereby closingand/or sealing the passage 92, as shown in FIG. 10D. In addition, ifdesired a sealant or other material may be introduced into the passage92 in conjunction with or separate from delivery of the clip 10 tofurther seal the passage 92, as is known to those skilled in the art.

Turning to FIGS. 11A-11C, another method is shown in which the apparatus50 may be used to deliver a clip 10, e.g., to engage intervening tissue96 to close and/or seal an incision, puncture, or other passage 92 thatextends from a patient's skin 94 through the intervening tissue 96, to awall 98 of the vessel 90. As shown in FIG. 11A, the sheath 52 may beinserted or otherwise positioned within the blood vessel 90, i.e.,through the passage 92. One or more devices (not shown) may be insertedthrough the sheath 52 to perform a procedure within the patient's body.After the procedure is complete, the device(s) may be removed from thesheath 52, and the sheath 52 may be manipulated to position the distalend 64 within the passage 92.

Turning to FIG. 11B, with the sheath 52 properly positioned, the housing54 may be actuated, for example, to advance the housing 54 distally intothe passage 92 to deliver the clip 10 to a location between thepatient's skin 94 and the vessel wall 98. The clip 10 may be deployedfrom the housing 54, thereby substantially engaging fascia or otherintervening tissue 96 with the tines 18. Once the clip 10 issuccessfully deployed within the passage 92, the apparatus 50 may bewithdrawn from the passage 92.

As shown in FIG. 11C, as the distal end 64 of the sheath 52 is withdrawnproximally from around the clip 10, the tines 18 of the clip 10 are freeto return towards the planar configuration. Because of the bias to theplanar configuration, the tines 18 automatically pull the tissuetogether, thereby closing and/or sealing the passage 92, as shown inFIG. 10D.

In a further alternative, shown in FIG. 12, a clip 450 may be providedthat includes a first set of tines 418 having a first length l₁, and asecond set of tines 419 having a second length l₂ substantially shorterthan the first length l₁. During use, similar to one of the methodsdescribed above, the clip 450 may be deployed such that the first set oftines 418 penetrate into and/or engage the wall of a blood vessel orother body lumen (not shown), while the second set of tines 418 engageextra-vascular tissue, i.e., tissue between the vessel wall and thepatient's skin. Thus, the clip 450 may simultaneously close both theopening in the vessel wall and the passage through the interveningtissue.

Turning to FIG. 13, another embodiment of a clip 510 is shown forengaging tissue, in accordance with the present invention. The clip 510includes a peripheral body 512 and a plurality of tissue engagingportions 514. Each tissue engaging portion 514 includes a pair of legs516 terminating in a tine 518 configured for penetrating or otherwiseengaging tissue. The tissue engaging portions 514 are disposedsubstantially symmetrically about a central axis 524. The body 512 alsocan include a plurality of expandable cells 520 that are connected byhinged regions 522 that also connect adjacent tissue engaging portions514, the cells 520 behaving similar to the embodiments described above.

In another embodiment, the body 512 and tissue engaging portions 514 areintegrally formed from a single sheet of material, such as a Nitinol,similar to the embodiments described above. The clip 510 is shown in arelaxed state with the tissue engaging portions 514 disposed radiallyoutward in a substantially planar configuration. Similar to the previousembodiments, the tissue engaging portions 514 may be deflected such thatthey extend from the body 512 substantially transversely with respectthe plane defined by the sheet (similar to FIG. 1B).

The tissue engaging portions 514 can be biased from the transverseconfiguration away from one another, i.e., towards the planarconfiguration. Thus, with the tissue engaging portions 514 in thetransverse configuration, the tines 518 may be engaged with tissue. Whenthe clip 510 is released, e.g., from within a delivery device, thetissue engage portions 514 may attempt to return to the planarconfiguration, thereby securing the tissue with respect to the clip 510.

In addition, the clip 510 may include expandable cells 520 that areexpandable from a compressed state to an expanded state (similar to FIG.1C), similar to the previous embodiments. The expandable cells 520 canbe biased to the expanded state, but may be compressed to the compressedstate, e.g., by constraining the clip 510. Alternatively, any of theclips described herein may be biased to the compressed state but may beexpanded to the expanded state, e.g., by constraining the clip over asheath or other elongate member.

Turning to FIG. 14, yet another embodiment of a clip 610 is shown thatincludes a peripheral body 612 and a plurality of tissue engagingportions 614 terminating in tines 618. The clip 610 may be formed from asingle sheet of material, such as Nitinol or may be formed from a wire,rod or tube (not shown), similar to the embodiments described above. Thetissue engaging regions 614 are disposed in opposing sets oriented awayfrom one another along an axis of symmetry 624, defining a substantiallyplanar configuration.

The tissue engaging portions 614 may be directed substantiallytransversely with respect to a plane defined by the planarconfiguration, for example, by loading the clip 614 into a housing orlumen of a delivery device (not shown). The tissue engaging portions 614can be biased to move away from one another, i.e., towards the planarconfiguration. In an alternative embodiment, the looped regions 626 orother regions of the body 612 may include expandable elements (notshown), e.g., having a zig-zag shape, a diamond shape, and the like.

Turning to FIG. 15, still another embodiment of a clip 710 is shown thatincludes a peripheral body 712 and a plurality of tissue engagingportions 714 terminating in tines 718. The clip 710 is similar to theprevious embodiment, except that the tissue engaging regions 714 aredisposed in opposing sets along an axis of symmetry 724, but areoriented in a common direction. The tissue engaging portions 714 may bedirected substantially transversely with respect to a plane defined bythe planar configuration. The tissue engaging portions 714 can be biasedto return towards the planar configuration shown. In an alternativeembodiment, the looped regions 726 or other regions of the body 712 mayinclude expandable elements (not shown), e.g., having a zig-zag shape, adiamond shape, and the like, similar to the previous embodiments.

The clip 710 may be constrained on a delivery apparatus (not shown),similar to that described above, such that the tissue engaging portions714 are all directed substantially transversely, and optionallydistally, to facilitate their engagement into tissue during deployment,as will be appreciated by those skilled in the art. Unlike previousembodiments, which may close tissue around an opening, this embodimentmay be useful when it is desired to maintain the relative position oftissue being engaged by the clip 710.

Turning now to the drawings, FIGS. 16A-16C show another embodiment of aclosure device or clip 810 for closing an incision, puncture, or otherpassage through tissue, e.g., communicating with a blood vessel or otherbody lumen (not shown). The clip 810 includes a body 812, which may begenerally annular in shape and surrounds a central axis 824, and aplurality of tines 818 extending from the body 812. As used herein, an“annular-shaped body” includes any hollow body, e.g., including one ormore structures surrounding an opening, whether the body issubstantially flat or has a significant thickness or depth. Thus,although an annular-shaped body may be circular, it may include othernoncircular shapes as well, such as elliptical or other shapes that areasymmetrical about a central axis.

The body 812 may include a plurality of looped or curved elements 828that are connected to one another to form the body 812. Each loopedelement 828 may include an inner or first curved region 832 and an outeror second curved region 34. In another embodiment, the first and secondcurved regions 832, 834 are out of phase with one another and areconnected alternately to one another, thereby defining an endlesssinusoidal pattern. Alternatively, other generally zigzag patterns maybe provided that repeat periodically, e.g., saw tooth or square toothpatterns (not shown), instead of a sinusoidal pattern, thereby defininginner and outer regions that alternate about the body 812. When the clip810 is in a substantially planar configuration, as shown in FIG. 16A,the first curved regions 832 may define an inner periphery 836 of thebody 812 and the clip 810, and the second curved regions 834 may definean outer periphery 838.

The plurality of tines 818 may be biased to extend generally inwardly,e.g., towards one another and/or towards the central axis 824. The tines818 may be disposed on the first curved regions 832, and oriented towardthe central axis 824 when the clip 810 is in the planar configuration.In another embodiment, the tines 818 may be provided in pairs oppositefrom one another or provided otherwise symmetrically with respect to thecentral axis 824.

The tines 818 may include a variety of pointed tips, such as a bayonettip, and/or may include barbs (not shown) for penetrating or otherwiseengaging tissue. For example, to increase the penetration ability of theclip 810 and/or to lower the insertion force required to penetratetissue, each tine 818 may include a tapered edge (not shown) extendingtowards the tip along one side of the tine 818. Alternatively, each tine818 may be provided with a tapered edge on each side of the tine 818extending towards the tip.

Additionally, as shown in FIGS. 16A-16C, the tines 818 may be disposedon alternating first curved regions 832. Thus, at least one period of azigzag pattern may be disposed between adjacent tines 818, which mayenhance flexibility of the clip 810, as explained further below.

As shown in FIGS. 16B and 16C (where opposite ends 833 a, 833 b areconnected to one another), the body 812 and/or the tines 818 may bedeflected such that the tines 818 extend transversely with respect tothe plane defined in the planar configuration, thereby defining atransverse configuration for the clip 810. The tines 818 can be orientedsubstantially parallel to the central axis 824 in the transverseconfiguration, as shown in FIG. 16B. In the transverse configuration,the body 812 may have a generally annular shape defining a length, L₁,which extends generally parallel to the central axis 824, andcorresponds generally to an amplitude of the zigzag pattern. The body812 can be sufficiently flexible such that the clip 810 may assume agenerally circular or elliptical shape (not shown), e.g., conforming toan exterior surface of a delivery device (not shown) used to deliver theclip 810.

In another embodiment, the tines 818 and/or body 812 are biased to movefrom the transverse configuration towards the planar configuration ofFIG. 16A. Thus, with the tines 818 in the transverse configuration, thetines 818 may penetrate and/or be engaged with tissue at a puncturesite. When the clip 810 is released, the tines 818 may attempt to returntowards one another as the clip 810 moves towards the planarconfiguration, thereby drawing the engaged tissue together andsubstantially closing and/or sealing the puncture site, as explainedfurther below.

The looped elements 828 may distribute stresses in the clip 810 as it isdeformed between the planar and transverse configurations, therebyminimizing localized stresses that may otherwise plastically deform,break, or otherwise damage the clip 810 during delivery. In addition,when the clip 810 is in the transverse configuration, the loopedelements 828 may be movable between a compressed state, such as thatshown in FIG. 16B, and an expanded state, such as that shown in FIG.16C. The looped elements 828 can be biased towards the expanded state,but may be compressed to the compressed state, e.g., by constraining theclip 810. Alternatively, only a portion of the looped elements 828 maybe biased towards the expanded state, e.g., the first curved regions832, and/or the looped elements 828 may be biased towards the compressedstate. Furthermore, the looped elements 828 reduce the force required tobe exerted on the clip 810 to transition the clip 810 from the planarconfiguration to the transverse configuration before loading onto adelivery device (not shown).

With the clip 810 in the transverse configuration, the looped elements828 may be circumferentially and/or radially compressed to thecompressed state until the clip 810 defines a first diameter orcircumference 826 a, such as that shown in FIG. 16B. The clip 810 may beconstrained in the compressed state, e.g., by loading the clip 10 onto acarrier assembly of a delivery device (not shown), as described furtherbelow. When released from the constraint, e.g., when deployed from thecarrier assembly, the clip 810 may automatically expand towards theexpanded state, such as that shown in FIG. 16C, thereby defining asecond diameter or circumference 826 b. Thus, the looped elements 828may facilitate reducing the profile of the clip 810 during delivery,e.g., to facilitate introducing the clip 10 through a smaller punctureor passage. Once the clip 810 is deployed entirely from the deliverydevice, the looped elements 828 may resiliently expand as the clip 810returns towards the planar configuration, as explained further below.

To manufacture the clip 810 (or, similarly, any of the other clipsdescribed herein), the body 812 and the tines 818 may be integrallyformed from a single sheet of material, e.g., a superelastic alloy, suchas a nickel-titanium alloy (“Nitinol”). Portions of the sheet may beremoved using conventional methods, such as laser cutting, chemicaletching, photo chemical etching, stamping, using an electrical dischargemachine (EDM), and the like, to form the clip. The tines 818 may besharpened to a point, i.e., tips may be formed on the tines 818 usingconventional methods, such as chemical etching, mechanical grinding, andthe like.

The clip 810 may be polished to a desired finish using conventionalmethods, such as electro-polishing, chemical etching, tumbling,sandblasting, sanding, and the like. Polishing may perform variousfunctions depending on the method used to form the clip 810. For a clipformed by laser cutting or using an EDM, polishing may remove heataffected zones (HAZ) and/or burrs from the clip. For a clip formed byphoto chemical etching, polishing may create a smoother surface finish.For a clip formed by stamping, polishing may remove or reduce burrs fromthe bottom side of the clip, and/or may smooth the “roll” that mayresult on the topside of the clip from the stamping process.

In addition or alternatively, the clip 810 may be formed from a shapememory alloy, e.g., Nitinol, with the looped elements 828 formedinitially in the compressed state and/or the clip 810 in the planarconfiguration. With the clip 810 deformed to the transverseconfiguration, the clip 810 may be expanded, e.g., by applying a forceradially outwards against an inner surface of the clip 810, therebyexpanding the looped elements 30 to the expanded state. The loopedelements 828 may then be heat treated, e.g., by heating the clip 10 toan austenitic state, to cause the looped elements 828 to “remember” theexpanded state, as is known to those skilled in the art. It may also benecessary to further heat treat the clip 810 further, e.g., with thetines in the planar configuration to cause the body 812 and/or tines 818to “remember” and be biased towards the planar configuration, as isknown to those skilled in the art. The clip 810 may then be cooled,e.g., to a martensitic state, which may be at or close to ambienttemperature, and manipulated, e.g., malleably deformed to the transverseconfiguration, for example, by loading the clip 810 onto a deliverydevice (not shown), as described below. Thus, if the clip 810 issubsequently heated to a predetermined temperature, e.g., at or belowbody temperature, the material may remember the planar configurationand/or expanded state and become biased towards them.

FIGS. 17A-17C show another embodiment of a closure device or clip 910that includes a generally annular-shaped body 912 defining a plane anddisposed about a central axis 9124 extending through the plane. The body912 can include a plurality of looped elements 928 that are connected toone another to form the body 912, similar to the previous embodiment.Each looped element 928 includes an inner or first curved region 932 andan outer or second curved region 934. Similar to the previousembodiment, the first and second curved regions 932, 934 may form anendless sinusoidal pattern or other generally zigzag pattern. When theclip 910 is in a substantially planar configuration, as shown in FIG.17A, the first curved regions 932 may define an inner periphery 936, andthe second curved regions 934 may define an outer periphery.

Unlike the previous embodiment, the clip 910 includes a plurality ofprimary tines 916 and a plurality of secondary tines 918. Each of theprimary and secondary tines 916, 918 may include a variety of knownpointed tips, similar to the previous embodiment.

Each of the primary tines 914 may have a length l₁, althoughalternatively each of the primary tines 914 may have a different lengththan one another. The primary tines 914 may be disposed in one or moreopposing pairs, e.g., on opposing first curved regions 932, and may beoriented towards and/or across the central axis 924 in the planarconfiguration. In the planar configuration, the lengths l₁ may besufficiently long such that the primary tines 914 at least partiallyoverlap one another, i.e., extend across the central axis 924 towards anopposing tine 914. Therefore, the tips of the primary tines 914 mayextend past the central axis 924 and/or the primary tines 914 in eachpair may lie substantially parallel to each other when the clip 910 isin the planar configuration.

Each of the secondary tines 916 may be disposed on a first or innercurved region 932, e.g., such that one or more secondary tines 916 maybe provided between opposing pairs of primary tines 914. Each of thesecondary tines 916 may have a length l.sub.2 that is substantially lessthan the length l₁ of the primary tines 914.

A secondary tine 916 can be is disposed on either side of each primarytine 914. For example, the clip 910 shown in FIGS. 17A-17C has first andsecond primary tines 914, and each of the first and second primary tines914 has a secondary tine 916 on either side of it. Thus, the clip 910may have a total of two primary tines 914 and four secondary tines 916.Optionally, the secondary tines 916 may be disposed substantiallysymmetrically about the central axis 924. The tines 914, 916 may beprovided on every other first curved regions 932. For example, a firstcurved region 932 having neither a primary tine 914 nor a secondary tine916 may separate each adjacent tine, e.g., between two adjacentsecondary tines 916, or between a secondary tine 916 and a primary tine914.

As shown in FIGS. 17B and 17C, the body 912 and/or the tines 914, 916may be deflected such that they extend transversely with respect to theplane defined in FIG. 17A. The primary tines 914 and secondary tines 916can be oriented substantially parallel to the central axis 924 to definea transverse configuration, as shown in FIG. 16B. In the transverseconfiguration, the body 912 has a generally annular shape defining alength, LE₁, which extends generally parallel to the central axis 924,and corresponds generally to an amplitude of the sinusoidal pattern. Thebody 912 can be sufficiently flexible such that the clip 910 may assumea generally circular or elliptical shape (not shown), e.g., conformingto an exterior surface of a delivery device (not shown).

The tines 914, 916 may be biased towards one another and/or towards thecentral axis 924, i.e., due to the bias of the clip 910 towards theplanar configuration of FIG. 17A, similar to the previous embodiment.With the clip 910 in the transverse configuration, the clip 910 may bedelivered such that the primary tines 914 entirely penetrate the wall ofa blood vessel or other body lumen, while the secondary tines 916 onlypartially penetrate the wall due to their relative lengths, as explainedfurther below.

The looped elements 928 may be expandable between a compressed state, asshown in FIG. 17B, and an expanded state, as shown in FIG. 17C, similarto the previous embodiment. The looped elements 928 can be biased to theexpanded state, but may be resiliently compressed to the compressedstate, e.g., by constraining the clip 910.

Turning to FIG. 18, an alternative embodiment of a clip 1010 is shownthat includes a body 912 including looped elements 930, and primarytines 914, similar to the previous embodiment, but has no supplementalor secondary tines 916. The reference numbers for elements of the clip1010 are consistent with like elements used for the clip 910.

Any of the clips of the present invention may include one or moreradiopaque markers or other markers visible using external imaging, suchas fluoroscopy. For example, using the clip 910 of FIGS. 17A-17C as anexample, the entire clip 910 may be coated with radiopaque material,which may be a high density material such as gold, platinum,platinum/iridium, and the like.

Alternatively, the clip 910 may be partially coated with radiopaquematerial by using masking techniques. For example, the entire clip 910may first be coated with radiopaque material. The clip 910 may then bemasked at locations where the radiopaque coating is desired. Forexample, the looped elements 928 of the clip 910 may be left unmaskedduring this process if it is desired to leave the looped elements 928uncoated by radiopaque material. This may be desirable, e.g., to preventradiopaque material from adversely affecting the flexibility of thelooped elements 928. The clip 910 may then be treated to remove theradiopaque material from the unmasked areas, in this example, the loopedelements 928. The masking may then be removed using conventionalprocesses, leaving the rest of the clip 910 coated with radiopaquematerial.

Turning to FIG. 19, in another alternative, one or more discrete markers902 may be provided at predetermined locations on the clip 910. Forexample, high density or radiopaque material 902 may be crimped orotherwise secured onto opposing double looped or circular regions 928.In another embodiment, shown in FIG. 20, a plurality of pockets 904 maybe provided on the looped elements 928 into which high density plugs(not shown) may be bonded or otherwise secured. These various radiopaquemarkers may also be incorporated in any of the embodiments describedherein.

Turning to FIG. 21, another embodiment of a clip 1110 is shown that,similar to clip 910, may include a plurality of looped elements 1128that interconnect to form a body 1112. Each looped element 1128 may havea first or inner curved region 1132 and a second or outer curved region1134. Primary tines 1114 may be disposed on opposing first curvedregions 1132, which, optionally, may include a barb 1102 thereon toenhance engagement with tissue. Secondary tines 1116 may be provided onfirst curved regions 1132 on either side of each primary tine 1114. Inaddition, a first curved region 1132 without a tine 1114, 1116 mayseparate adjacent tines, as described above with regard to the previousembodiments.

The clip 1110 also includes stop members 1106 on one or more of thetines 1114, 1116, e.g., adjacent the respective first curved region1132. Each stop member 1106 may be blunt-shaped, e.g., generallytriangularly with an apex 1107 of the stop member 1106 extending fromthe first curved region 1132, and the tine 1114, 1116 extending from awide or blunt base 1107 of the stop member 1106. During use, the bluntbases 1107 may limit penetration of the respective tines 1114, 1116 intotissue by reducing an effective length of the respective tine 1114,1116. For example, when the tines 1114, 1116 are driven into tissue, thetines 1114, 1116 may penetrate the tissue until the blunt bases 1107contact the tissue, whereupon the tines 1114, 1116 may be prevented frompenetrating further into the tissue.

Turning to FIG. 22, another embodiment of a clip 1210(i) is shown thatincludes a body 1212, a plurality of tines 1214, and a plurality ofspring elements 1240(i) that interconnect between adjacent tines 1214.The body 1212 includes outer curved regions 1234 that extend betweenadjacent tines 414, thereby defining an outer periphery for the clip1210(i). The clip 1210(i) may be moveable between a substantially planarconfiguration such as that shown in FIG. 22, and a transverseconfiguration (not shown), and can be biased towards the planarconfiguration, similar to the previous embodiments.

In the embodiment shown, the spring elements 1240(i) generally arehollow diamond shaped elements, including curved inner regions 1232(i)oriented towards the central axis 1224 of the body 1212 when the clip1210(i) is in the planar configuration. The spring elements 1240(i) mayserve multiple purposes. First, the spring elements 1240(i) may bias theclip 1210(i), e.g., allowing the clip 410(i) to at least partiallyexpand resiliently. For example, when the clip 1210(i) is deflected intothe transverse configuration (not shown), the spring elements 1240(i)may allow the tines 1214 to be moved away from the central axis 1224and/or one another. Thus, during deployment, the tines 1214 may bedeflected radially outwardly or otherwise expanded to engage a largerarea of tissue.

As the tines 414 are expanded, the spring elements 1214(i) may deform tobecome wider (along a dimension extending generally between the adjacenttines 1214) and shorter (along a dimension extending generally parallelto the tines 1214). Once a force causing the tines 1214 to expand isremoved, the spring elements 1214(i) may resiliently try to returntowards their original shape, thereby pulling the tines 1214 closertowards one another.

In addition, the curved inner regions 1232(i) of the spring elements1214(i) may provide stops limiting penetration of the tines 1214 intotissue, similar to the stop members described above. For example, whenthe clip 1210(i) is in the transverse configuration and the springelements 1214(i) are expanded, the curved inner regions 1232(i) may bebecome more oblique, possibly becoming generally linear. Thus, when thetines 1214 are driven into tissue, the curved inner regions 1232(i) maylimit penetration of the tines 1214.

Finally, after the clip 1210(i) is deployed, e.g., the tines 1214 arepenetrated into tissue, the curved inner regions 1232(i) may returntowards their original shape, and may pinch or otherwise engage tissuebetween the inner curved regions 1232(i) and the adjacent tines 1214.Thus, contracting the spring elements 1240(i) may enhance the ability ofthe clip 1210(i) to seal a puncture site, e.g., by pulling engagedtissue inwardly towards the central axis 1224 of the clip 1210(i).

Turning to FIG. 23, an alternative embodiment of a clip 1210(ii) isshown that is substantially similar to the clip 1210(i) shown in FIG.22, with the exception of the shape of the spring elements 1240(ii).Rather than diamond shaped elements, the spring elements 1240(ii) arelooped elements generally defining a circular shape.

Turning now to FIG. 27, another embodiment of a clip 1510 of the presentinvention is illustrated. Similar to the previous embodiments, the clip1510 includes a generally annular-shaped body 1512 that defines a plane.The body 1512 is disposed about a central axis 1524 that extends throughthe plane. The body 1512 can include a plurality of outer curvedelements 1528 that extend between adjacent tines 1516 and are connectedto each other to form the body 1512. When the clip 1510 is in asubstantially planar configuration, as shown in FIG. 27, the curvedelements 1528 define an outer periphery 1538 of the clip 1510.

The tines 1516 are curved or arcuately shaped and include distal tips1515 that extend toward the central axis 1524 when the clip 1510 is inthe substantially planar configuration. Optionally, one or more of thetines 1516 may include barbs 1517, similar to the previous embodiments.The curve of the tines 1516 can all be in phase with one another suchthat the tines 1516 spiral about the central axis 1524. This may allow alength of the tines 1516 to be maximized for a given diameter of thebody 1512.

For example, the tines 1516 may have a length that is greater than aradius of the body 1512 without the distal tips 1515 of the tines 1516touching one another. Thus, due to the arcuate shape of each tine 1516,the tines 1516 of clip 1510 may be generally longer than the straighttines of the previous clips having comparable diameters. The tines 1516may, therefore, penetrate deeper into tissue than the tines of the otherclips.

As with the previous embodiments, the body 1512 and/or the tines 1516 ofclip 1510 may be deflected until the tines 1516 extend transversely withrespect to the plane defined in the planar configuration, therebydefining a transverse configuration. In the transverse configuration,the tines 1516 may be oriented substantially parallel to the centralaxis 1524. Additionally, as with the previous embodiments, the tines1516 and/or body 1512 may be biased to move from the transverseconfiguration towards the planar configuration. The clip 1510 may bedelivered in substantially the same manner as will be described withrespect to other clips of the present invention.

Any of the clips of the present invention may be coated with a substancethat enhances hemostasis and/or healing of a blood vessel, e.g., byincreasing a rate of regeneration of endothelium on the interior surfaceof the vessel, or by decreasing inflammatory response at the treatmentsite. In one embodiment, a suitable synthetic peptide coating may beapplied to a clip to attract endothelial cells to the surface. Anexemplary synthetic peptide coating may, for example, attach to the samecell binding sites as collagen. In another embodiment, a clip may becoated with a combination of clotting factors in order to promotehemostasis. For example, one side of the clip may be coated with FactorIII and an endopeptidase, such as PTA, to accelerate the intrinsicclotting pathway. On the opposite side of the clip, a combination of aprotein cofactor proaccelerin (Factor V) and an activated endopeptidase,such as serum prothrombin conversion accelerator (SPCA),cothromboplastin, and the like, may be applied to accelerate theextrinsic clotting pathway. The clips of the present invention may alsobe coated with any suitable hydrophilic polymer that swells in thepresence of bodily fluids in order to reduce, minimize, or stop bloodflow, thereby aiding the hemostasis process.

The clips of the present invention may be delivered using variousapparatus and methods. An exemplary apparatus 1300 suitable fordelivering a clip of the present invention is shown in FIG. 24. Othersuitable apparatus that may be used to deliver a clip of the presentinvention are disclosed in U.S. Pat. No. 6,942,674, which is assigned tothe assignee of the present application, the disclosures of which, andany references therein, are incorporated herein in their entirety bythis reference.

Generally, the apparatus 1300 includes an introducer sheath 1352, and ahousing or carrier assembly 1354 slidably disposed on the sheath 1352.The sheath 1352 includes a substantially flexible or semi-rigid tubularbody 1358 including a lumen 1360 extending between its proximal anddistal ends 1362, 1364. The distal end 1364 has a size and shapeconfigured to facilitate insertion into a blood vessel, e.g., having atapered tip for facilitating substantially atraumatic introductionthrough the passage and at least partially into the vessel. The lumen1360 has a size for inserting one or more devices therethrough, such asa catheter, guidewire, and the like (not shown). The sheath 1352 alsocan include one or more seals (not shown), such as a hemostatic valve,within the lumen 1360 at or near the proximal end 1362 that provides afluid-tight seal, yet accommodates inserting one or more devices intothe lumen 1360 without fluid passing proximally from the sheath 1352.

Optionally, the sheath 1352 may include a side port 1366 thatcommunicates with the lumen 1360, for example, to deliver fluids intothe lumen 1360. Alternatively, or in addition, the side port 1366 may beused to provide a “bleed back” indicator. An exemplary “bleed back”indicator and related methods of use are disclosed in U.S. Pat. No.6,626,918, which is assigned to the assignee of the present application,the disclosures of which, and any references therein, are incorporatedherein in their entirety by this reference.

The apparatus 1300 may also include a mechanical locator or obturator1400, such as that disclosed in U.S. application Ser. No. 10/081,723,now U.S. Pat. No. 6,942,674, the disclosures of which, and anyreferences therein, are incorporated herein in their entirety by thisreference, that may be part of an actuator assembly that is attachableto the proximal end of the sheath 1352. Alternatively, the mechanicallocator or obturator 1400 may be a separate device that is insertableinto the lumen 1360, e.g., through the actuator assembly. Generally, theobturator 1400 is an elongate member including a distal tip 1414 and adistal portion 1416. The distal tip 1414 may be substantially softand/or flexible such that the distal tip 1414 may substantiallyatraumatically enter the vessel 1390 (not shown, see FIGS. 25A-25D). Thedistal portion 1416 generally includes one or more wings or otherexpandable elements 1418 for providing tactile feedback, as describedfurther below.

The carrier assembly 1354 is slidably disposed on an exterior of thesheath 1352, and is configured for releasably carrying a clip 910 (shownin phantom), which may any of the clips described herein. The carrierassembly 1354 may be substantially permanently attached to the sheath1352 and/or may be actuated from the proximal end 1362 of the sheath1352, for example, by the actuator assembly (not shown), to advance theclip 910 distally during deployment. Alternatively, the clip 910 may becarried by an actuator assembly, as disclosed in co-pending U.S.application Ser. No. 10/081,725, now U.S. Pat. No. 6,749,621, filed onthe same day as the present application and entitled “Sheath Apparatusand Methods for Delivering a Closure Device,” which is assigned to theassignee of the present application, the disclosures of which, and anyreferences therein, are incorporated herein in their entirety by thisreference.

Turning to FIGS. 25A-D, the apparatus 1300 may be used to deliver theclip 910 to close and/or seal an incision, puncture, or other passage1392 that extends from a patient's skin 1394, through intervening tissue1396, and into a wall 1398 of a vessel 1390 or other body lumen.Alternatively, the apparatus 1300 may be used to deliver the clip 910 toengage tissue in other procedures, e.g., to connect tissue segmentstogether or otherwise to secure tissue structures with respect to oneanother. For example, the apparatus 1300 and clip 910 may be used toattach an anastomosis during a bypass procedure. It will be appreciatedby those skilled in the art that the clip 910 and/or apparatus 1300 maybe useful in a variety of procedures.

As shown in FIG. 25A, the sheath 1352 may be inserted or otherwisepositioned within the vessel 1390, i.e., through the passage 1392. Thesheath 1352 may be advanced over a guidewire or other rail (not shown)previously positioned through the passage 1392 into the vessel 1390 oradvanced in conjunction with a pointed stylet directly through tissueusing conventional procedures. The vessel 1390 can be a peripheralvessel, such as a femoral, radial, or carotid artery, although otherbody lumens may be accessed using the sheath 1352, as will beappreciated by those skilled in the art.

The passage 1392, and consequently the sheath 1352, may be oriented atan angle “alpha” with respect to the vessel 1390, thereby facilitatingintroducing devices through the lumen 1360 of the sheath 1352 into thevessel 1390 with minimal risk of damage to the vessel 1390. One or moredevices, such as a guide wire, a catheter, and the like (not shown), maybe inserted through the sheath 1352 and advanced to a desired locationwithin the patient's body. For example, the devices may be used toperform a therapeutic or diagnostic procedure, such as angioplasty,atherectomy, stent implantation, and the like, within the patient'svasculature.

After the procedure is complete, any devices used during the proceduremay be removed from the sheath 1352, and the obturator 1400 may beinserted into the lumen 1360. For example, the obturator 1400 may bepart of an actuator assembly (not shown), and may be advanced throughthe lumen when the actuator assembly is attached to the proximal end ofthe sheath 1352. Alternatively, the actuator assembly and obturator 1400may be coupled separately to the sheath 1352.

When the obturator 1400 is fully inserted within the sheath 1352, thedistal portion 1416 of the obturator 1400 may extend beyond the distalend 1364 of the sheath 1352. In an alternative embodiment, the obturator1400 may be attached to an exterior surface (not shown) of the sheath1352, for example, along a track, e.g., including cooperating slots,grooves, and the like (not shown) in the sheath 1352 and obturator 1400.

Turning to FIG. 25B, the expandable elements 1418 on the distal portionof the obturator 1400 may then be directed to their expandedconfiguration, for example, by activating a switch on the proximal end(not shown) of the obturator 1400. With the sheath 1352 and obturator1400 coupled to one another, the sheath 1352 and obturator 1400 may bemoved in conjunction with one another.

As shown in FIG. 25C, the sheath 1352 may be partially withdrawn fromthe vessel 1390, until the expandable elements 1418 contact the wall1398 of the vessel 1390. Thus, the expandable elements 1418 may providea tactile indication of the position of the sheath 1352 with respect tothe wall 1398 of the vessel 1390. In addition, the expandable elements1418 may assist in “presenting” the wall 1398 of the vessel 1390, e.g.,for receiving the clip 910.

Generally, the clip 910 is carried by the carrier assembly 1354 beforethe procedure. The clip 910 may be constrained in its transverseconfiguration on the carrier assembly 1354, and the carrier assembly1354 may be provided on or adjacent the proximal end of the sheath 1352.Because the tines, which may include primary and secondary tines 914,916 may be biased towards one another, the tines 914, 916 may slidablycontact an inner surface (not shown) of the carrier assembly 1354 or anouter surface of the sheath 1352, thereby constraining the clip 910 inits transverse configuration.

Turning to FIG. 25D, with the sheath 1352 properly positioned, thecarrier assembly 1354 may then be actuated, for example, to advance thecarrier assembly 1354 distally over the sheath 1352 to deliver the clip910. The carrier assembly 1354 may only be advanced a predeterminedfixed distance relative to the distal end of the sheath 1352, andconsequently, the expandable elements 1418 of the obturator 1400, suchthat the clip 910 substantially engages the wall 1398 of the bloodvessel 1390. This predetermined distance may facilitate properlydeploying the clip 910 with respect to the wall 1398 of the vessel 1390,e.g., to prevent advancing the clip 910 too far, i.e., into the vessel1390.

As the clip 910 is deployed from the carrier assembly 1354, the clip 910may be expanded to an enlarged diameter. For example, a distal end ofthe carrier assembly 1354 may include a ramped region (not shown) thatmay deflect the tines 914, 916, and/or the body of the clip 910 radiallyoutwardly. As the clip 910 is advanced over the ramped region, the tines914, 916 may be deflected radially outwardly as they are being driveninto the surrounding tissue, thereby engaging a larger region of tissuethan if the tines 914, 916 had been maintained substantially axially.

Alternatively, the clip 910 may include expandable looped elementsand/or spring elements (not shown), such as those described above, thatmay facilitate expanding the clip 910 as it is deployed from the carrierassembly 1354 and/or the sheath 1352. For example, the looped elementsof the clip 910 may be compressed when the clip 910 is loaded into thecarrier assembly 1354, e.g., thereby allowing a relatively smallerprofile carrier assembly 1354 to be used. The clip 910 may automaticallyexpand upon deployment from the carrier assembly 1354 to engage a largerregion of tissue surrounding the opening, such as an arteriotomy 1391 inthe wall 1398 of the vessel 1390 (see FIG. 26A).

Once the clip 910 is deployed entirely or otherwise released from thesheath 1352, the clip 910 may resiliently move towards its substantiallyplanar configuration, such as that shown in FIG. 26B.

During delivery of the clip 910, radiopaque markers (not shown) on theclip 910, the carrier assembly 1354, and/or the expandable members 1418may be monitored, e.g., using fluoroscopy, to facilitate observingand/or positioning the apparatus 1300. Thus, a relative position of theclip 910 with respect to the expandable elements 1418, and consequentlyto the wall 1398 of the vessel 1390, may be ascertained before the clip910 is deployed from the carrier assembly 1354.

Turning to FIGS. 26A and 26B, in another embodiment, the expandableelements 1418 of the obturator 1400 may be rotationally offset from theone or more tines 914 on the clip 910. For example, if the clip 910includes primary tines (such as those shown in FIGS. 17A and 18), theobturator 600 and clip 910 may have a predetermined relative angularorientation about the central axis 924. The clip 910 can be loaded ontothe carrier assembly 1354 in a predetermined angular orientation and theobturator 600 is receivable in the sheath 1352 only in a predeterminedangular orientation that is offset such that the tines 914, 916 are outof axial alignment with the expandable elements 1418, as shown in FIG.26A.

This predetermined rotational orientation may substantially minimize thepossibility of the primary tines 914 contacting and/or damaging theexpandable elements 1418. For example, with particular reference to FIG.26A, a relative angular orientation of the clip 910 and obturator 1400is shown relative to an arteriotomy 591 in the wall 598 of the vessel590. Here, the expandable elements 618 are oriented to crisscrossdiagonally the arteriotomy 591 within the interior of the vessel 590.Generally, because of the natural structure of the tissue in the wall ofa vessel, an arteriotomy generally tends to adopt an elongate shape thatextends transversely to the direction of flow (i.e., across thecircumference of the vessel wall).

The primary tines 914 are oriented such that the primary tines 914pierce the wall 1398 of the vessel 1390 on either side of thearteriotomy 1391, as shown. With the expandable elements 1418crisscrossing diagonally, risk of contact with the primary tines 914 issubstantially reduced. Thus, the primary tines 914 may be sufficientlylong to extend entirely through the wall 1398 of the vessel 1390 whileavoiding the expandable elements 618.

The expandable elements 1418 may then be collapsed and/or withdrawn intothe distal end 1364 of the sheath 1352. As the clip 910 is releasedentirely from the sheath 1352, the primary tines 914 may partiallyoverlap, as shown in FIG. 26B, thereby pulling the arteriotomy 1391closed, similar to a single-thread suture. For example, the expandableelements 1418 may be automatically collapsed immediately before or afterthe clip 910 is deployed from the carrier assembly 1354 or when thecarrier assembly 1354 reaches its extreme distal position. The distalportion 1416 of the obturator 1400 can be collapsed and retracted intothe sheath 1354 after the primary tines 914 have pierced the wall 1398of the vessel 1390, but before the clip 910 is entirely released fromthe sheath 1352.

In addition, if the clip 910 includes secondary tines 916 (such as thoseshown in FIG. 17A), the secondary tines 916 may partially penetrate thewall 1398 of the vessel 1390 during deployment of the clip 910. Thelengths of the secondary tines 916 can be relatively short or stopmembers (not shown) may be provided that prevent the secondary tines 916from piercing entirely through the wall 1398. When the clip 910 isreleased, the secondary tines 916 may pull the tissue inwardly, behavingsomewhat similarly to a purse-string suture, to enhance closing thearteriotomy 1391.

Once the clip 910 is successfully deployed into the wall 1398 of thevessel 1390, e.g., on either side of an arteriotomy 1391, the apparatus1300 may be withdrawn from the passage 1392. The entire apparatus 1300may be removed in one step, or alternatively, the obturator 1400 mayfirst be withdrawn from the sheath 1352 before withdrawing the sheath1352, thereby leaving the clip 910 in place to close the arteriotomy1391 and/or seal the passage 1392. In addition, if desired, a sealant orother material may be introduced into the passage 1392 in conjunctionwith or separate from delivery of the clip 910 to further seal thepassage 1392, as is known to those skilled in the art.

According to another aspect, the clips described herein can bemanufactured in various manners. These clips can be useful for engagingtissue so as to connect tissue segments together or to close and/or sealopenings through tissue such as a puncture wound in a body lumen. Theseclips may be used by deforming them from their generally planarconfiguration such that the tines are pointing in a direction generallytransverse to the plane, holding the clip in this deformed condition,deploying the clip proximal to the tissue to be engaged and removing thedeforming force such that the clip engages the tissue and attempts toreturn to its original generally planar configuration. The methods andapparatus disclosed in the above-mentioned U.S. patent application Ser.Nos. 10/081,726 and 09/732,178, now U.S. Pat. Nos. 6,623,510 and6,719,777 can be used to deploy the clips of the present invention toengage tissue and close or seal an opening.

In such use, the deformation of the clip causes the tines to be directedgenerally axially away from the body of the clip and it is the elasticproperty of the deformed clip which causes it to attempt to return toits original generally planar configuration. The body of the device maycomprise a series of looped elements which generally define an endlesszigzag pattern, e.g., a sinusoidal pattern, extending about a centralaccess. The looped elements are believed to facilitate deforming thedevice between the planar and transverse configurations, e.g., bydistributing stresses through the device and minimizing localizedstresses in the curved regions.

In another embodiment of the present invention, a clip precursor isfirst formed from a sheet of material, such as a superelastic alloy,such as a nickel-titanium alloy (“Nitinol”) alloy. The property ofsuperelasticity and of certain alloys which possess that property isdisclosed in U.S. Pat. No. 4,665,906, the disclosures of which, and anyreferences therein, are incorporated herein in their entirety by thisreference. This forming can be done by removing portions of the materialby cutting, chemical etching, laser cutting, photochemical etching,stamping, electrical discharge machining and the like to produce aprecursor such as that shown in FIG. 28A which has radially outwardextending tines. The precursor can then be polished using one or moreprocesses such as electropolishing, tumbling, sand blasting, sanding andthe like or such polishing can be done as a final step after the clip isformed. Forming of a precursor in this manner does not require workingto tolerances as close as those which would be required if the clip wasto be manufactured in its final configuration shown in FIG. 28B becausethe radially outwardly extending tines of the precursor shown in FIG.28A are easily accessible by the forming tool whereas attempting todirectly form the clip with radially inwardly extending tines which areclosely spaced requires difficult high precision metal cutting. Thus,manufacture of a precursor which is then reconfigured to final clipshape permits the achievement of closer spacing between the elements ofthe final clip than would otherwise be achievable with conventionalmethods.

The precursor 1610 comprises a hoop-shaped planar body 1611 which hasoutwardly extending primary (longer) tines 1612 and secondary (shorter)tines 1613. For example, the primary trials may be 0.070 to 0.105 inchesin length and the secondary tines may be 0.025 to 0.035 inches inlength. Each of the tines terminates in a point 1614. When the precursor1610 has been reconfigured into clip 1616 shown in FIG. 28B, the tines1612 and 1613 become the tissue engaging portions of the clip. The tinesmay be sharpened or given a shape, e.g., barbs (not shown), while thedevice is in the precursor state. The body 1611 may compromiseconnecting links such as loops 1615. These links may have any suitableshape provided that such shape does not interfere with inversion of theprecursor 1610.

The precursor 1610 is then inverted to reconfigure it into the shape ofclip 1616. In this embodiment in which the precursor is formed from asheet of nickel-titanium alloy, the inverted precursor is then heat set,e.g., by heating to a temperature of 510° C., and then quenched to coolto room temperature. The clip 1616 will now be in the austenitic state.

Heat setting and quenching are essential to successful practice of theinvention with superelastic alloys. As explained in more detail in U.S.Pat. No. 4,665,906, the disclosures of which, and any referencestherein, are incorporated herein in their entirety by this reference, asuperelastic alloy such as nickel-titanium exists in two states, theaustenitic state and the martensitic state. Such alloys will initiallybe in the austenitic state, e.g., when the precursor is formed. However,when the precursor is inverted to take the shape of the final clip, thestress experienced by the alloy during the inversion will cause thealloy to be partially or wholly converted to the martensitic state. Sucha martensitic state is commonly referred to as stress-inducedmartensite. Such martensite structure has the property ofsuperelasticity and the inverted precursor would revert to its originalshape if not held in the inverted configuration.

Since, if the inverted precursor was left in the martensitic state, itwould want to elastically revert to its original uninverted state, itmust be converted back to austenite. Thus, heating and quenching arerequired to convert the inverted precursor from the martensitic state tothe austenitic state such that the clip is stable in its planarconfiguration as shown in FIG. 28B and will retain that configuration.

The times and temperatures for heat setting of superelastic alloys ofvarious compositions can be determined from existing literature or canbe determined empirically without any difficulty. The clips are small insize and the heating and quenching may be done with any conventionalheating and quenching equipment. For example, once inverted, theinverted precursor can be held in that configuration and placed in afixture which will hold it in the inverted configuration during heatsetting.

When clips are manufactured according to the present invention, thespace between the tines may actually be eliminated, i.e., afterinverting the precursor, the tines may be in contact with each other, ineither a side-by-side or an over-and-under relationship. The number,length and spacing of the tines may be varied according to the desiresof the manufacturer. Furthermore, while use of a planar precursor is aconvenience in manufacturing, a planar configuration is not required.For example, the precursor could be bent along a diameter or major orminor axis of the precursor and could be heat set in such a bentconfiguration. Alternatively, the clip, while generally planar, may havethe tines extending at an acute angle to the plane defined by the bodyas shown in FIG. 31 in which the body 1611 and tines 1612 are shown.Furthermore, manufacturing from a sheet of material is a convenience,but other manufacturing techniques, including joining of components suchas the tines to the body, can be accomplished by welding, brazing, orother known methods of joining materials. In such cases, one or more ofsuch components may be circular in cross-section or tubular inconfiguration.

Still further, the clip need not be fabricated from a single material,e.g., the tines may be manufactured from a different material than thebody. In such cases, a portion of the clip such as the tines may bebioabsorbable provided that the final clip is capable of elasticrecovery after being deformed. An advantage of the present invention isthat it permits the production of clips with tines that are 30 to 40% ormore longer than those which could be made with prior direct cuttingmethods, because there is no limit on the length of the tine which isformed on the precursor. Thus, after the precursor is inverted, thetines may overlap the annular body.

In the alternative embodiment of this invention illustrated in FIGS. 29Aand 29B, the precursor 1620 is manufactured in an expanded oversizeconfiguration to provide space for removing material from a sheet ofmaterial, such as a superelastic alloy, such as nickel-titanium, byconventional methods such as cutting, chemical etching, photochemicaletching, stamping, electric discharge machining, laser cutting or thelike.

The precursor 1620 is reconfigured by imposing radially inwardlydirected force on body 1621 such that precursor 1620 takes a smallerplanar shape such as one of those shown in FIG. 29B. The precursor 20has a planar body 1621, tines 1622 and 1623 having points 1624 and suchtines are connected by links 1625 as previously described with regard toFIG. 28A. The reconfigured precursor is then heat set and quenched asdescribed above to complete the manufacture of clip 1626.

Clips of still other configurations can be manufactured in the manner ofclip 1626 by starting with a differently shaped precursor such asprecursor 1630 shown in FIG. 30A. Precursor 1630 can be reconfigured bybeing subjected to radially inward deforming forces as shown in FIG. 30Bor by opposed laterally inward forces as shown in FIG. 30C. In eachcase, the planar body 1631 having tines 1632 and 1633 with points 1634and links 1635 will be caused to take a smaller dimension and will beheat set as described above to form clips 1636 and 1637. Clipsmanufactured according to the method of the present invention can have amultitude of configurations other than those shown in FIGS. 28B, 29B,and 30C and 30D. For example, the configurations shown in U.S. patentapplication Ser. Nos. 09/732,178 and 10/081,726, now U.S. Pat. Nos.6,719,777 and 6,623,510, could be manufactured according to the presentinvention.

It has been found that Nitinol sheet is stronger in one direction thanin others, which may be the result of crystal orientation in theNitinol. The clip precursors can be formed such that the primary tinesare aligned with the strongest orientation of the Nitinol. It has beenfound, as shown in FIG. 7, that the greatest strength of the primarytines is achieved if those tines are transverse to the grain orientationof the Nitinol. Thus, FIG. 34 illustrates clip precursor 1660 havingprimary tines 1661 as the precursor would be cut from sheet 1662. Thegrain orientation of sheet 1662 is shown by the double-headed arrow1663. Typically, a plurality of precursors 1660 would be cut from thesame sheet, each with its primary tines transverse to the grainorientation of the sheet. In addition, even if clips are formed directlywithout using precursors, it is desirable that their primary tines betransverse to the grain orientation.

The clips of the present invention may have primary or secondary tineswhich have the same or different lengths and the tines may be straightor curved. For example, radially opposed tines may have one tine at “12o'clock” which is longer than the opposing tine at “6 o'clock.”Exemplary configurations of clip precursors with primary tines ofdifferent length are shown in FIGS. 32 and 33. In FIG. 32, clipprecursor 1640 is shown with a primary tine 1641 which is shorter thanprimary tine 1642. Similarly, in FIG. 33, a clip precursor is shownwhich has a primary tine 1651 which is shorter than primary tine 1652.

The clips of the present invention may also be delivered using theapparatus and methods described in U.S. patent application Ser. No.10/081,723, filed Feb. 21, 2002, now U.S. Pat. No. 6,942,674, which isassigned to the assignee of the present application, the disclosures ofwhich, and any references therein, are incorporated herein in theirentirety by this reference. Similarly, the apparatus and methodsdisclosed in U.S. patent application Ser. No. 10/081,717, filed Feb. 21,2002, now U.S. Pat. No. 6,695,867, which is assigned to the Assignee ofthe present application, the disclosures of which, and any referencestherein, are incorporated herein in their entirety by this reference.

Other features can be added to the clips including radio-opaque markers,and/or porous surfaces to promote tissue ingrowth or the clip may becoated in whole or in part with a bioabsorbable material and/or coatedwith a material containing a substance which is delivered to the patientfor therapeutic, diagnostic or other purposes. Such coatings maycomprise peptides, clotting factors or other materials designed tobenefit the patient.

While the principal object of the present invention is to provide amanufacturing method which facilitates the production of clips having asmall footprint, the present invention can also be used to make clips oflarger dimensions since, no matter what methods are used to cut theprecursor from a sheet of material, the ease of manufacture of evenlarger size clips is facilitated. Thus, the advantages of the presentinvention may be realized with regard to clips having larger sizes andclips having a variety of configurations.

Turning now to the drawings, FIGS. 35A-35C show another embodiment of aclosure device or clip 1710 for closing an incision, puncture, or otherpassage through tissue, e.g., communicating with a blood vessel or otherbody lumen (not shown). The clip 1710 includes a body 1712, which may begenerally annular in shape and surrounds a central axis 1724, aplurality of primary tines 1714 and a plurality of secondary tines 1716extending from the body 1712. As used herein, an “annular-shaped body”includes any hollow body, e.g., including one or more structuressurrounding an opening, whether the body is substantially flat or has asignificant thickness or depth. Thus, although an annular-shaped bodymay be circular, it may include other noncircular shapes as well, suchas elliptical or other shapes that are asymmetrical about a centralaxis.

The body 1712 includes a plurality of looped or curved elements 1728that are connected to one another to form the body 1712. Each loopedelement 1728 may include an inner or first curved region 1732 and anouter or second curved region 1734. In another embodiment, the first andsecond curved regions 1732, 1734 are out of phase with one another andare connected alternately to one another, thereby defining an endlesssinusoidal pattern. Alternatively, other generally zigzag patterns maybe provided that repeat periodically, e.g., saw tooth or square toothpatterns (not shown), instead of a sinusoidal pattern, thereby defininginner and outer regions that alternate about the body 1712.

The plurality of tines 1714 and 1716 may be biased to extend generallyinwardly, e.g., towards one another and/or towards the central axis1724. The tines 1714 and 1716 may be disposed on the first curvedregions 1732, and oriented toward the central axis 1724 when the clip1710 is in the planar configuration. The primary tines 14 are offsetfrom the axis of symmetry 1737 of the loops from which they extend andare connected to a first curved region 1732 by a straight connectingelement having a longer side 1735 and a shorter side 1736. In anotherembodiment, the tines 14 and 1716 may be provided in pairs opposite fromone another or provided otherwise symmetrically with respect to thecentral axis 1724.

The tines 1714 and 1716 may include a variety of pointed tips, such as abayonet tip, and/or may include barbs (not shown) for penetrating orotherwise engaging tissue. For example, to increase the penetrationability of the clip 1710 and/or to lower the insertion force required topenetrate tissue, each primary tine 1714, as shown in FIG. 35A aselement 1718, and each secondary tine 1716 may include a tapered edge(not shown) extending towards the tip along one side of the tine 1714 or1716. Alternatively, as shown in FIGS. 35A-35C, each tine 1714 or 16 maybe provided with a tapered edge on each side of the tine 1714 or 1716extending towards the tip.

Additionally, as shown in FIGS. 35A-35C, the tines 1714 and 1716 may bedisposed on alternating first curved regions 1732. Thus, at least oneperiod of a zigzag pattern may be disposed between adjacent tines 1714and 1716, which may enhance flexibility of the clip 1710, as explainedfurther below.

As shown in FIGS. 35B and 35C (where opposite ends 1733 a, 1733 b areconnected to one another), the body 1712 and/or the tines 1714 and 1716may be deflected such that the tines 1716 extend transversely withrespect to the plane defined in the planar configuration, therebydefining a transverse configuration for the clip 1710. The tines 1714and 1716 can be oriented substantially parallel to the central axis 1724in the transverse configuration, as shown in FIG. 35B. In the transverseconfiguration, the body 1712 may have a generally annular shape defininga length, LE₁, that extends generally parallel to the central axis 1724,and corresponds generally to an amplitude of the zigzag pattern. Thebody 1712 can be sufficiently flexible such that the clip 1710 mayassume a generally circular or elliptical shape (not shown), e.g.,conforming to an exterior surface of a delivery device (not shown) usedto deliver the clip 1710.

In another embodiment, the tines 1714 and 1716 and/or body 1712 arebiased to move from the transverse configuration towards the planarconfiguration of FIG. 35A. Thus, with the tines 14 and 16 in thetransverse configuration, the tines 1714 and 1716 may penetrate and/orbe engaged with tissue at a puncture site. When the clip 1710 isreleased, the tines 1714 and 1716 may attempt to return towards oneanother as the clip 1710 moves towards the planar configuration, therebydrawing the engaged tissue together and substantially closing and/orsealing the puncture site, as explained further below.

The looped elements 1728 may distribute stresses in the clip 1710 as itis deformed between the planar and transverse configurations, therebyminimizing localized stresses that may otherwise plastically deform,break, or otherwise damage the clip 1710 during delivery. In addition,when the clip 1710 is in the transverse configuration, the loopedelements 1728 may be movable between a compressed state, such as thatshown in FIG. 35B, and an expanded state, such as that shown in FIG.35C. The looped elements 1728 can be biased towards the expanded state,but may be compressed to the compressed state, e.g., by constraining theclip 1710. Alternatively, only a portion of the looped elements 1728 maybe biased towards the expanded state, e.g., the first curved regions1732, and/or the looped elements 1728 may be biased towards thecompressed state. Furthermore, the looped elements 1728 reduce the forcerequired to be exerted on the clip 1710 to transition the clip 1710 fromthe planar configuration to the transverse configuration before loadingonto a delivery device (not shown).

With the clip 1710 in the transverse configuration, the looped elements1728 may be circumferentially and/or radially compressed to thecompressed state until the clip 1710 defines a first diameter orcircumference 1726 a, such as that shown in FIG. 35B. The clip 1710 maybe constrained in the compressed state, e.g., by loading the clip 1710onto a carrier assembly of a delivery device (not shown), as describedfurther below. When released from the constraint, e.g., when deployedfrom the carrier assembly, the clip 1710 may automatically expandtowards the expanded state, such as that shown in FIG. 35C, therebydefining a second diameter or circumference 1726 b. Thus, the loopedelements 1728 may facilitate reducing the profile of the clip 1710during delivery, e.g., to facilitate introducing the clip 1710 through asmaller puncture or passage. Once the clip 1710 is deployed entirelyfrom the delivery device, the looped elements 1728 may resilientlyexpand as the clip 1710 returns towards the planar configuration, asexplained further below.

To manufacture the clip 1710 (or, similarly, any of the other clipsdescribed herein), the body 1712 and the tines 1714 and 1716 may beintegrally formed from a single sheet of material, e.g., a superelasticalloy, such as Nitinol. Portions of the sheet may be removed usingconventional methods, such as laser cutting, chemical etching, photochemical etching, stamping, using an electrical discharge machine (EDM),and the like, or the method disclosed in U.S. patent application Ser.No. 10/335,075, filed Dec. 31, 2002, to form the clip. The tines 1714and 1716 may be sharpened to a point, i.e., tips may be formed on thetines 1714 and 1716 using conventional methods, such as chemicaletching, mechanical grinding, and the like.

The clip 1710 may be polished to a desired finish using conventionalmethods, such as electro-polishing, chemical etching, tumbling,sandblasting, sanding, and the like. Polishing may perform variousfunctions depending on the method used to form the clip 1710. For a clipformed by laser cutting or using an EDM, polishing may remove heataffected zones (HAZ) and/or burrs from the clip. For a clip formed byphoto chemical etching, polishing may create a smoother surface finish.For a clip formed by stamping, polishing may remove or reduce burrs fromthe bottom side of the clip, and/or may smooth the “roll” that mayresult on the topside of the clip from the stamping process.

In addition or alternatively, the clip 1710 may be formed from a shapememory alloy, e.g., Nitinol, with the looped elements 1728 formedinitially in the compressed state and/or the clip 1710 in the planarconfiguration. With the clip 1710 deformed to the transverseconfiguration, the clip 1710 may be expanded, e.g., by applying a forceradially outwards against an inner surface of the clip 1710, therebyexpanding the looped elements 1728 to the expanded state. The loopedelements 1728 may then be heat treated, e.g., by heating the clip 1710to an austenitic state, to cause the looped elements 1728 to “remember”the expanded state, as is known to those skilled in the art. It may alsobe necessary to further heat treat the clip 1710 further, e.g., with thetines in the planar configuration to cause the body 1712 and/or tines1714 and 1716 to “remember” and be biased towards the planarconfiguration, as is known to those skilled in the art. The clip 1710may then be cooled, e.g., to a martensitic state, which may be at orclose to ambient temperature, and manipulated, e.g., malleably deformedto the transverse configuration, for example, by loading the clip 1710onto a delivery device (not shown), as described below. Thus, if theclip 1710 is subsequently heated to a predetermined temperature, e.g.,at or below body temperature, the material may remember the planarconfiguration and/or expanded state and become biased towards them.

Each of the primary tines 1714 may have a length l₁, althoughalternatively, as shown in FIG. 35A, each of the primary tines 1714 mayhave a different length than one another. The primary tines 1714 may bedisposed in one or more opposing pairs, e.g., on opposing first curvedregions 1732, and may be oriented towards and/or across the central axis1724 in the planar configuration. In the planar configuration, thelengths l₁ may be sufficiently long such that the primary tines 1714 atleast partially overlap one another, i.e., extend across the centralaxis 1724 towards an opposing tine 1714. Therefore, the tips of theprimary tines 1714 may extend past the central axis 1724 and/or theprimary tines 14 in each pair may lie substantially parallel to eachother when the clip 1710 is in the planar configuration.

Each of the secondary tines 16 may be disposed on a first or innercurved region 32, e.g., such that one or more secondary tines 16 may beprovided between opposing pairs of primary tines 14. Each of thesecondary tines 16 may have a length l₂ that is substantially less thanthe length l₁ of the primary tines 14.

A secondary tine 1716 can be disposed on either side of each primarytine 1714. For example, the clip 1710 shown in FIGS. 35A-35C has firstand second primary tines 1714, and each of the first and second primarytines 1714 has a secondary tine 1716 on either side of it. Thus, theclip 1710 may have a total of two primary tines 1714 and four secondarytines 1716. Optionally, the secondary tines 1716 may be disposedsubstantially symmetrically about the central axis 1724. The tines 1714,1716 may be provided on every other first curved regions 1732. Forexample, a first curved region 1732 having neither a primary tine 1714nor a secondary tine 1716 may separate each adjacent tine, e.g., betweentwo adjacent secondary tines 16, or between a secondary tine 16 and aprimary tine 1714.

With the clip 1710 in the transverse configuration, the clip 1710 may bedelivered such that the primary tines 1714 entirely penetrate the wallof a blood vessel or other body lumen, while the secondary tines 1716only partially penetrate the wall due to their relative lengths, asexplained further below.

As shown in FIG. 35A, primary tines 1714 are connected to curved regions1732 by linear regions 1735 and 1736 which are of different lengths.Thus, primary tines 1714 are offset from the axis of symmetry 1737 ofthe loops having the curved regions to which they are attached. Theoffsetting of primary tines is also disclosed in parent application Ser.No. 10/335,075, filed Dec. 31, 2002, which discloses the use of curvedconfigurations to connect the primary tines to the curved regions of theclip. It has been found desirable to use linear, or straight, regions,as shown as elements 1735 and 1736 in FIG. 35A to connect the primarytines 1714 of the present invention to the curved regions 1732.

FIG. 36 illustrates a clip of the same general type as that of FIG. 35A,but in a somewhat different embodiment in which primary tines 1714 aoverlap body 1712 at locations comprising first curved regions 1732.

FIGS. 37A-37C illustrate various designs of clips configured accordingto the present invention in which the primary tines, which are offsetfrom the axis of symmetry of the loop from which they extend, areconnected directly to a first curved region or are connected to thecurved region by extending one side of the curved region to form oneside of the primary tine and connecting the other side of the primarytine with a curved connecting element.

Turning to FIGS. 37A-37C in more detail, FIG. 37A illustrates clip 1826has body 1821, primary tines 1822, secondary tines 1823 and loops 1825.Each loop has an axis of symmetry such as that indicated by 1827. Thetines are provided with point 1824. In this embodiment, the primarytines 1822 are offset from the axis of symmetry of the loop from whichthey extend and are connected directly to the first curved section ofsuch loop.

In FIG. 37B, the clip 1936 has body 1931 having primary tines 1932 andsecondary tines 1933 is illustrated. The body 1931 is provided withloops 1935 and the primary tines 1932 comprise a first side 1937 whichis an extension of a side of the loop 1938 from which tine 1937 extendsand another side 1939 which is connected directly to the loop from whichit extends. The primary tines are offset from the axis of symmetry,indicated by 1940 of the loop from which they extend.

The clip of FIG. 37C is similar in some respects to the clip of 37B, butis generally elliptical in shape rather than generally circular inshape. Thus, clip 2037 comprises body 2031 which has loops 2035, primarytines 2032, secondary tines 2033 which tines have points 2034. In thisembodiment, the primary tines 2032 extend beyond the innermost reach ofthe first curved regions which are opposite the first curved regionsfrom which the primary tines extend. The primary tines are offset fromthe axis of symmetry 2038 of the loop from which they extend. Theprimary tines of the clip of FIG. 37C are connected to the loops fromwhich they extend in the same manner as those of FIG. 37B.

FIG. 38 illustrates a clip 2110 in which the primary tines 2114 and 2116are of different lengths. The primary tines 2114 and 2116 are offsetfrom the axis of symmetry 2130 of the loop from which they extend andare connected to the loop in the same manner as the primary tines ofFIG. 37B.

Any of the clips of the present invention may include one or moreradiopaque markers or other markers visible using external imaging, suchas fluoroscopy. For example, using the clip 1710 of FIGS. 35A-35C as anexample, the entire clip 1710 may be coated with radiopaque material,which may be a high density material such as gold, platinum,platinum/iridium, and the like.

Alternatively, the clip 1710 may be partially coated with radiopaquematerial by using masking techniques. For example, the entire clip 1710may first be coated with radiopaque material. The clip 1710 may then bemasked at locations where the radiopaque coating is desired. Forexample, the looped elements 1728 of the clip 1710 may be left unmaskedduring this process if it is desired to leave the looped elements 1728uncoated by radiopaque material. This may be desirable, e.g., to preventradiopaque material from adversely affecting the flexibility of thelooped elements 1728. The clip 1710 may then be treated to remove theradiopaque material from the unmasked areas, in this example, the loopedelements 1728. The masking may then be removed using conventionalprocesses, leaving the rest of the clip 1710 coated with radiopaquematerial.

In another alternative, one or more discrete markers may be provided atpredetermined locations on the clip 1710. For example, high density orradiopaque material may be crimped or otherwise secured onto opposingdouble looped or circular regions 1728. In another embodiment, aplurality of pockets may be provided on the looped elements 1728 intowhich high density plugs (not shown) may be bonded or otherwise secured.These various radiopaque markers may also be incorporated in any of theembodiments described herein.

Any of the clips of the present invention may be coated with a substancethat enhances hemostasis and/or healing of a blood vessel, e.g., byincreasing a rate of regeneration of endothelium on the interior surfaceof the vessel, or by decreasing inflammatory response at the treatmentsite. In one embodiment, a suitable synthetic peptide coating may beapplied to a clip to attract endothelial cells to the surface. Anexemplary synthetic peptide coating may, for example, attach to the samecell binding sites as collagen. In another embodiment, a clip may becoated with a combination of clotting factors in order to promotehemostasis. For example, one side of the clip may be coated with FactorIII and an endopeptidase, such as PTA, to accelerate the intrinsicclotting pathway. On the opposite side of the clip, a combination of aprotein cofactor proaccelerin (Factor V) and an activated endopeptidase,such as serum prothrombin conversion accelerator (SPCA),cothromboplastin, and the like, may be applied to accelerate theextrinsic clotting pathway. The clips of the present invention may alsobe coated with any suitable hydrophilic polymer that swells in thepresence of bodily fluids in order to reduce, minimize, or stop bloodflow, thereby aiding the hemostasis process.

As described herein, the clips of the present invention may be deliveredusing various apparatus and methods. Suitable apparatus that may be usedto deliver a clip of the present invention are disclosed in U.S.application Ser. No. 10/081,723, filed on Feb. 21, 2002, now U.S. Pat.No. 6,942,674, and entitled “Apparatus and Methods for Delivering aClosure Device” and in U.S. application Ser. No. 10/356,214, filed Jan.30, 2003, and Ser. No. 10/638,115, filed Aug. 8, 2003, and Ser. No.10/081,725, filed Feb. 2, 2001, now U.S. Pat. No. 6,749,621, which areassigned to the assignee of the present application, the disclosures ofwhich, and any references therein, are incorporated herein in theirentirety by this reference.

While the invention is susceptible to various modifications, andalternative forms, specific examples thereof have been shown in thedrawings and are herein described in detail. It should be understood,however, that the invention is not to be limited to the particular formsor methods disclosed, but to the contrary, the invention is to cover allmodifications, equivalents and alternatives falling within the spiritand scope of the appended claims. For example, and not by way oflimitation, the features and structures of one clip can be used with anyother clip described herein. Similarly, the structures and methodsuseable to deploy a clip can be used to deploy other clips, including,but not limited to, those clips described herein.

What is claimed is:
 1. A medical device comprising: a plurality of strutmembers generally biased to a deployed configuration to form a pluralityof generally diamond-shaped openings in an annular shaped structure withthe generally diamond-shaped openings extending generally longitudinallyrelative to a longitudinal axis of the medical device; and a pluralityof tissue engaging portions disposed at a distal portion of the medicaldevice, each tissue engaging portion extending generally distallytowards the longitudinal axis in a deployed configuration.
 2. Themedical device of claim 1, wherein each generally diamond-shaped openinghas a mid-portion having a width in a direction transverse to alongitudinal axis of the generally diamond-shaped opening greater thanwidths of a remainder of the generally diamond-shaped opening.
 3. Themedical device of claim 1, wherein each tissue engaging portion extendsaway from the generally diamond-shaped opening to engage tissue disposedadjacent to the tissue engaging portion.
 4. The medical device of claim1, wherein the plurality of tissue engaging portions are disposedsubstantially symmetrically about the longitudinal axis.
 5. The medicaldevice of claim 1, wherein the generally diamond-shaped openings arebiased toward an expanded, deployed configuration.
 6. The medical deviceof claim 1, wherein two adjacent struts of the plurality of struts arecoupled together at a hinged region.
 7. The medical device of claim 1,wherein the medical device includes 5 or more diamond-shaped openings.8. The medical device of claim 1, wherein the plurality of tissueengaging portions extend distally from a proximal end of the pluralityof generally diamond-shaped openings.
 9. A medical device comprising: aplurality of generally diamond-shaped openings formed from a pluralityof curved elements generally biased to a deployed configuration, theplurality of curved elements being configured to position the pluralityof generally diamond-shaped openings in an annular arrangement; and aplurality of tissue penetrating portions, each tissue penetratingportion being disposed between adjacently positioned generallydiamond-shaped openings and extending from a junction of adjacent curvedelements of the plurality of curved elements at a location spaced apartfrom an apex of the generally diamond-shaped openings.
 10. The medicaldevice of claim 9, wherein each generally diamond-shaped opening isconfigured to receive tissue.
 11. The medical device of claim 9, whereinthe plurality of curved elements are formed of a shape memory material.12. The medical device of claim 9, wherein the plurality of curvedelements collectively forms a plurality of spring elements configured tomove the plurality of tissue penetrating portions.
 13. The medicaldevice of claim 9, wherein each apex is a tissue engaging portion. 14.The medical device of claim 13, wherein the apices being spacedsubstantially symmetrically about an axis of the medical device.
 15. Themedical device of 13, wherein each apex is a hinged region.